Early detection presents new opportunities to slow or perhaps even halt Alzheimer’s disease progression

 

Researchers from the Rowan University School of Osteopathic Medicine are nearing development of a blood test that can accurately detect the presence of Alzheimer's disease, which would give physicians an opportunity to intervene at the earliest, most treatable stage. Robert Nagele, PhD, presented his team's most recent findings October 18 at OMED 15 in Orlando. Dr. Nagele's work focuses on utilizing autoantibodies as blood-based biomarkers to accurately detect the presence of myriad diseases and pinpoint the stage to which a disease has progressed. By detecting Alzheimer's disease long before symptoms emerge, Dr. Nagele hopes those with disease-related autoantibody biomarkers will be encouraged to make beneficial lifestyle changes that may help to slow development of the disease. "There are significant benefits to early disease detection because we now know that many of the same conditions that lead to vascular disease are also significant risk factors for Alzheimer's. People found to have preclinical disease can take steps to improve their vascular health, including watching their diet, exercising and managing any weight and blood pressure issues to help stave off or slow disease progression," Nagele said. While the cause of Alzheimer's remains elusive, it is clear that maintaining a healthy blood-brain barrier is a critical preventative measure. Diabetes, high cholesterol, high blood pressure, stroke and being overweight jeopardize vascular health. As blood vessels in the brain weaken or become brittle with age, they begin to leak, which allows plasma components including brain-reactive autoantibodies into the brain. There, the autoantibodies can bind to neurons and accelerate the accumulation of beta amyloid deposits, a hallmark of Alzheimer's pathology. The blood test developed by Dr. Nagele has also shown promise in detecting other diseases, including Parkinsons's, multiple sclerosis and breast cancer. His team's research on the role of autoantibodies explains that: All humans possess thousands of autoantibodies in their blood; These autoantibodies specifically bind to blood-borne cellular debris generated by organs and tissues all over the body; An individual's autoantibody profile is strongly influenced by age, gender and the presence of specific diseases or injuries; and Diseases cause characteristic changes in autoantibody profiles that, when detected, can serve as biomarkers that reveal the presence of the disease. In Alzheimer's, the brain begins to change years before symptoms emerge. Detecting Alzheimer's antibodies at the preclinical stage would give patients an opportunity to work with their physician to make lifestyle changes or receive available treatments before they become symptomatic. Potentially, this early intervention could help those with preclinical Alzheimer's avoid or delay the most devastating symptoms. "As osteopathic physicians, we constantly tell patients that a healthy lifestyle is the best medicine for preventing disease. We also know that many people tune out messages about nutrition and exercise until a health crisis gets their attention," said Jennifer Caudle, DO, assistant professor of family medicine at Rowan University. "I can't think of a single patient who wouldn't take steps to prevent the progression of Alzheimer's if they could directly affect their prognosis." Dr. Nagele's research has been supported by grants from the Michael J. Fox Foundation and the Osteopathic Heritage Foundation.   http://www.sciencedaily.com/releases/2015/10/151018075617.htm

Clues to keeping brain cells alive in those with Alzheimer's

 

A drug may be able to make it easier to learn a language, sharpen your memory and help those with dementia and Alzheimer's disease. (Stock image) Credit: © kenwnj / Fotolia Can you imagine a drug that would make it easier to learn a language, sharpen your memory and help those with dementia and Alzheimer's disease by rewiring the brain and keeping neurons alive? New Rutgers research published in the Journal of Neuroscience found that a drug -- RGFP966 -- administered to rats made them more attuned to what they were hearing, able to retain and remember more information, and develop new connections that allowed these memories to be transmitted between brain cells. "Memory-making in neurological conditions like Alzheimer's disease is often poor or absent altogether once a person is in the advanced stages of the disease," said Kasia M. Bieszczad, lead author and assistant professor in Behavioral and Systems Neuroscience in the Department of Psychology. "This drug could rescue the ability to make new memories that are rich in detail and content, even in the worst case scenarios." What happens with dementias such as Alzheimer's is that brain cells shrink and die because the synapses that transfer information from one neuron to another are no longer strong and stable. There is no therapeutic treatment available that reverses this situation. The drug being tested in this animal study is among a class known as HDAC inhibitors -- now being used in cancer therapies to stop the activation of genes that turn normal cells into cancerous ones. In the brain, the drug makes the neurons more plastic, better able to make connections and create positive changes that enhance memory. Researchers found that laboratory rats, taught to listen to a certain sound in order to receive a reward, and given the drug after training, remembered what they learned and responded correctly to the tone at a greater rate than those not given the drug. Scientists also found that the rodents were more "tuned in" to the relevant acoustic signals they heard during their training -- an important finding Bieszczad said because setting up the brain to better process and store significant sounds is critical to human speech and language. "People learning to speak again after a disease or injury as well as those undergoing cochlear implantation to reverse previous deafness, may be helped by this type of therapeutic treatment in the future," said Bieszczad "The application could even extend to people with delayed language learning abilities or people trying to learn a second language." This hypersensitivity in processing auditory information enabled the neurons to reorganize and create new pathways -- allowing more of the information they learned to become a long-term memory, said Bieszczad who collaborated with colleagues in the Department of Neurobiology and Behavior at the University of California Irvine. "People normally remember an experience with limited detail -- not everything we see, hear and feel is remembered," she said. "What has happened here is that memory becomes closer to a snapshot of the actual experience instead of being sparse, limited or inaccurate." Story Source: The above post is reprinted from materials provided by Rutgers University.Note: Materials may be edited for content and length. Journal Reference: K. M. Bieszczad, K. Bechay, J. R. Rusche, V. Jacques, S. Kudugunti, W. Miao, N. M. Weinberger, J. L. McGaugh, M. A. Wood. Histone Deacetylase Inhibition via RGFP966 Releases the Brakes on Sensory Cortical Plasticity and the Specificity of Memory Formation. Journal of Neuroscience, 2015; 35 (38): 13124 DOI: 10.1523/JNEUROSCI.0914-15.2015   http://www.sciencedaily.com/releases/2015/10/151002113548.htm

Alzheimer's: Dealing with family conflict

 

Alzheimer's disease can cause stress for families. Work through family conflicts together so that you can focus on what's important. By Mayo Clinic Staff When a loved one is diagnosed with Alzheimer's disease, the effects on the family can be overwhelming. The reality that someone you care for has Alzheimer's can trigger a range of emotions — including anger, fear, frustration and sadness. Conflicts are common as family members struggle to deal with the changes. To minimize conflict, address the issues together. Share responsibility When figuring out how you're loved one will be cared for, consider each family member's preferences, resources and abilities. Some might provide hands-on care, either in their own homes or in your loved one's home. Others might be more comfortable with respite care, household chores or errands. You and your family might also choose someone to handle financial or legal issues. Meet regularly To stay on top of your loved one's care, plan regular family meetings. Include everyone who's part of the caregiving team, including family friends and other close contacts. You might also share email updates with the entire family, or send updates through social media resources. During family meetings, discuss each person's caregiving responsibilities and challenges — and make changes as needed. Be open to compromise and possibilities you hadn't considered on your own. If your family meetings tend to turn into arguments, consider asking a counselor, social worker, mediator or other professional to moderate. Next Sept. 05, 2015 References See more In-depth Página 2 Be honest To help diffuse any tension, talk about your feelings in an open, constructive manner. If you're feeling stressed or overwhelmed, say so — and then work together to brainstorm more effective ways to share the burden of your loved one's care. Again, work with a professional if needed. Be careful to express your feelings without blaming or shaming anyone else. Use "I" statements, such as "I'm having trouble juggling my own schedule with all of dad's appointments." Keep an open mind as you listen to other family members share their thoughts and feelings. Don't criticize There are many "right" ways to provide care. Respect each caregiver's abilities, style and values. Be especially supportive of family members responsible for daily, hands-on care. Consider counseling If you're concerned that the stress of Alzheimer's will tear your family apart, seek help. You might join a support group for Alzheimer's caregivers, seek family counseling or ask for advice from your care team. Remember, working through conflicts together can help you move on to more important things — caring for your loved one and enjoying your time together as much as possible. Sep. 05, 2015 References See more In-depth http://www.mayoclinic.org/healthy-lifestyle/caregivers/in-depth/alzheimers/art-20047365/

Fatty Acids in the Brain Hasten Alzheimer’s

 

Fri, 08/28/2015 - 5:30pm Greg Watry, Digital Reporter People with Alzheimer's disease have fat deposits in the brain. For the first time since the disease was described 109 years ago, researchers affiliated with the University of Montreal Hospital Research Centre (CRCHUM) have discovered accumulations of fat droplets in the brain of patients who died from the disease and have identified the nature of the fat. Image: Meritxell Garcia, CC by-nc-ndIn 1906 at the 37th Conference of South-West German Psychiatrists in Tübingen, German physician Dr. Alois Alzheimer elucidated symptoms of a disease that would later be named after him. He described the case of 51-year-old woman Auguste D., and her progressive symptoms of cognitive impairment, hallucinations and delusions. According to the Alzheimer’s Association, upon autopsy of Auguste D.’s brain, Alzheimer found “dramatic shrinkage and abnormal deposits in and around nerve cells.” According to the World Health Organization (WHO), 47.5 million people worldwide have dementia, with Alzheimer’s disease responsible for between 60 and 70% of cases. According to research published in Cell Stem Cell, accumulations of fat droplets in the brain, which have been identified in deceased patients, may spur and hasten the development of the disease. Researchers affiliated with the Univ. of Montreal Hospital Research Centre found significantly more fat droplets in the brains of nine patients with Alzheimer’s disease when compared with five healthy brains. A team of chemists used advanced mass spectrometry, and identified the fat deposits as “triglycerides enriched with specific fatty acids, which can also be found in animals fats and vegetable oils,” according to the university. “We discovered these fatty acids are produced by the brain, that they build up slowly with normal aging, but that the process is accelerated significantly in the presence of genes that predispose to Alzheimer’s disease,” said co-author Karl Fernandes. “In mice predisposed to the disease, we showed these fatty acids accumulate very early on, at two months of age, which corresponds to the early twenties in humans. Therefore, we think that the build-up of fatty acids is not a consequence. but rather a cause of accelerator of the disease.” Pharmacological inhibitors of fatty acid-producing enzymes do exist. Such molecules are being tested to determine their efficacy against fighting obesity.     According to Fernandes, the team successfully prevented the accumulation of fatty acids in the brains of mice predisposed to Alzheimer’s. “It significantly increased stem cell activity,” said Fernandes. “This is very promising because stem cells play an important role in learning, memory and regeneration.” The university said the study supports the idea Alzheimer’s is a metabolic brain disease. Currently, no treatments exist to suppress the disease’s progression, or reverse it, according to the WHO.   http://www.rdmag.com/articles/2015/08/fatty-acids-brain-hasten-alzheimers

Alzheimer's: Understand wandering and how to address it

 

Alzheimer's causes disorientation, which can lead to wandering. Here's how to curb or prevent wandering, as well as ensure a safe return if your loved one is lost. By Mayo Clinic Staff Alzheimer's Caregiving Subscribe to our Alzheimer's Caregiving e-newsletter to stay up to date on Alzheimer's topics. Wandering or getting lost is common among people with dementia. This behavior can happen at any stage of Alzheimer's. If your loved one has Alzheimer's, he or she is at risk of getting lost — even if he or she has never wandered in the past. Understand wandering There are many reasons why a person who has Alzheimer's might wander, including: Stress or fear. Your loved one might wander as a reaction to an unfamiliar or overstimulating environment, a loud noise or a situation he or she doesn't understand. Searching. He or she might get lost while searching for someone or something. Boredom. He or she might be looking for something to do. Basic needs. He or she might be looking for a bathroom or food, or want to go outdoors. Following past routines. He or she might try to go to work, do chores or buy groceries. Prevent wandering Wandering is not necessarily harmful if it occurs in a safe and controlled environment. However, wandering can pose safety issues. To prevent unsafe wandering identify why the wandering might be happening. For example, if your loved one tends to wander at the same time every day or when he or she is bored, plan meaningful activities to keep him or her better engaged. If your loved one is searching for a spouse or child, post a sign stating that the person in question will be visiting soon to provide reassurance and reduce wandering. Keep your loved one safe It's not always possible to prevent wandering. To keep your loved one safe: Reduce hazards. Remove tripping hazards, such as throw rugs and extension cords. Install night lights to aid nighttime wanderers. Put gates at stairwells to prevent falls. Install alarms and locks. Various devices can alert you that your loved one is on the move. You might place pressure-sensitive alarm mats at the door or at your loved one's bedside, put warning bells on doors and use childproof covers on doorknobs. If your loved one tends to unlock doors, you might install sliding bolt locks out of your loved one's line of sight. Camouflage doors. Place removable curtains over doors or camouflage doors with paint or wallpaper that matches the surrounding walls. Signs on doors might help, too. Use a GPS device. Consider having your loved one wear a GPS or other tracking device that can send electronic alerts about his or her location. If your loved one wanders, the GPS device can help you find him or her quickly. Ensure a safe return Wanderers who get lost can be difficult to find because they often react unpredictably. For example, they might not call for help or respond to searchers' calls. Once found, wanderers might not remember their names or where they live. If you're concerned about your loved one's wandering, inform the local police, your neighbors and other close contacts about your loved one's condition. Keep a list of emergency phone numbers handy in case you can't find your loved one. Keep a recent photo of your loved one on hand, too. Also consider enrolling in the Alzheimer's Association safe-return program. For a small fee, participants receive an identification bracelet and access to 24-hour support in case of emergency. If your loved one is lost, contact local authorities and the safe-return program — if you've enrolled — right away. The sooner you ask for help, the sooner your loved one is likely to be found.

Families affected by early alzheimer's seek better treatment

 

Mon, 07/20/2015 - 11:30am Lauran Neergaard, AP Medical Writer Giedre Cohen, 37, of Calabasas, Calif., and Carrie Richardson, 34, of Montgomery, Ala., pose for a picture during a break at the Alzheimer's Association International Conference in Washington, Saturday, July 18, 2015. Saturday for the first time, researchers brought together dozens of these families with the very rarest form of Alzheimer's, young and inherited--patients, patients-to-be and their healthy loved ones _ from as far as Australia and Britain to meet face-to-face. (AP Photo/Manuel Balce Ceneta)Alzheimer's has ravaged generations of Dean DeMoe's family - his grandmother, father, siblings - all in their 40s and 50s. DeMoe himself inherited the culprit gene mutation and at 53, the North Dakota man volunteers for a drug study he hopes one day will end the family's burden. International scientists gathering in Washington for a conference this week express cautious optimism that they may finally be on the right track to fight Alzheimer's. Families like DeMoe's with the very rarest form of Alzheimer's, young and inherited, hold crucial clues to fighting this brain-destroying disease in everyone. On Saturday, researchers for the first time brought together dozens of these families - patients, patients-to-be and their healthy loved ones - from as far as Australia and Britain to meet face to face. They shared advice about when their children should undergo gene testing to learn their own fate, and they got an unusual opportunity to grill government and drug company officials about why it's taking so long to find a good treatment. "Finally, I got to talk to other people who are going through the same thing," said DeMoe, of Thompson, North Dakota, who with four other siblings inherited the family's bad gene. One sister was spared. His wife, Deb, said he experiences early memory changes known as mild cognitive impairment, but DeMoe still holds a job with an oil company and said, "I don't dwell on it." Families' first question: Why not try to fix the gene defect that causes this form of Alzheimer's instead of targeting its downstream effects? Why, asked others, can't desperate families get faster access to experimental drugs, as AIDS patients once did? "It's time to ease our anguish," said Tal Cohen of Calabasas, California. At age 37, his wife, Giedre, already is in the mild-to-moderate stage of Alzheimer's. He emerged hopeful that researchers are considering creative ways to speed that access. "We don't have any more time to wait and see," he said. Alzheimer's usually strikes older adults, affecting about 1 in 9 people age 65 or over. Less than 1 percent of cases worldwide are the autosomal dominant form, caused by inheriting a gene with a particular mutation that triggers the disease well before the senior years. Children of an affected parent have a 50 percent chance of inheriting their family's bad gene. But if they do, they almost always get sick about the same time their parent did. Many of these families are part of the Dominantly Inherited Alzheimer Network (DIAN) study that monitors the health of family gene carriers and their healthy relatives in several countries. Recently, it showed that silent changes in the brain can precede the first memory problems by 20 years. Now scientists think the best hope against Alzheimer's is to treat high-risk people long before symptoms appear, aiming to at least stall the disease if not prevent it. On Sunday, researchers at the Alzheimer's Association International Conference reported possible new ways to predict who will get sick with the more common late-onset Alzheimer's - vital to testing such treatments - and a single test probably won't be enough, said Johns Hopkins University neuroscientist Marilyn Albert. Tracking about 350 people starting in middle age, Albert's team found a combination of tests predicted development of mild cognitive impairment within five years. They include a spinal tap to measure toxic levels of Alzheimer's hallmark amyloid and tau proteins; MRI scans to detect shrinking brain regions; and two standard memory assessments. The combination isn't ready for doctors' offices, but should help drug companies tell who to enroll in early-stage treatment studies, she said. Scientists at VU University Medical Center in Amsterdam found another protein, named neurogranin, in spinal fluid. It may signal that connections called synapses are dying, making it harder for brain cells to communicate. -Researchers at the University of Alberta, Canada, are beginning to hunt a saliva test for earlier markers of cognitive decline. But knowing who is destined for Alzheimer's and approximately when it will strike makes rare families such as DeMoe's especially critical for research. A second DIAN study now is testing whether either of two experimental drugs might give those gene carriers more symptom-free years by fighting buildup of sticky amyloid in the brain. That study soon will expand to test additional drugs. "The goal here really is to get drugs approved to help everyone," said Dr. Randall Bateman of Washington University in St. Louis, who oversees the DIAN drug study. Dean DeMoe came to the meeting with his wife, healthy sister and two of his three children. He wishes researchers could have revealed if those drugs are working, but they won't know for several years. Meanwhile, his two oldest children, in their 20s, had gene testing as part of health-tracking research but chose not to be told the results until they are older or protective drugs come along. His teenager thinks she will make the same choice. DeMoe pins his hopes on the drug study. "It might not do good for me," he said, "but it's important for my family and for everyone." Source: Associated Press

Study authors say its likely protective effect comes from antihypertensive drugs

 

A new study suggests that people with a genetic predisposition to high blood pressure have a lower risk for Alzheimer's disease. However, authors conclude the connection may have more to do with anti-hypertension medication than high blood pressure itself. "It's likely that this protective effect is coming from antihypertensive drugs," said co-author John Kauwe, associate professor of biology at Brigham Young University. "These drugs are already FDA approved. We need to take a serious look at them for Alzheimer's prevention." The study, published this month in PLOS Medicine, analyzed genetic data from 17,008 individuals with Alzheimer's and 37,154 people without the disease. Data came from the Alzheimer's Disease Genetics Consortium and the International Genomics of Alzheimer's Project. BYU researchers worked with scholars from the University of Cambridge, Aarhus University in Denmark and the University of Washington on the massive study. BYU's role was to flex its muscles in supercomputing and bioinformatics. With the help of BYU's supercomputer, Kauwe and undergraduate student Kevin Boehme pieced together 32 data sets for the analysis. The research team looked for links between Alzheimer's disease and a number of health conditions -- including diabetes, obesity, and high cholesterol -- but only found a significant association between higher systolic blood pressure and reduced Alzheimer's risk. (A weak connection between smoking and Alzheimer's also surfaced.) "Our results are the opposite of what people might think," said fellow co-author Paul Crane, a University of Washington associate professor of internal medicine. "It may be that high blood pressure is protective, or it may be that something that people with high blood pressure are exposed to more often, such as antihypertensive medication, is protecting them from Alzheimer's disease." University of Cambridge senior investigator scientist Robert Scott led the study, which used "Mendelian randomization" to find if the risk factors (BMI, insulin resistance, blood pressure, cholesterol, diabetes) for Alzheimer's had a causal impact. Mendelian randomization uses subjects' genetics as a proxy for a randomized clinical trial. "This is to date the most authoritative paper looking at causal relationships between Alzheimer's disease and these potentially modifiable factors," Kauwe said. "In terms of the number of samples, it can't get bigger at this point."

New potential cause for Alzheimer's: Arginine deprivation caused by overconsumption by immune cells

 

A new Duke University study in mice suggests that in Alzheimer's disease, certain immune cells that normally protect the brain begin to abnormally consume an important nutrient: arginine. Blocking this process with a small-molecule drug prevented the characteristic brain plaques and memory loss in a mouse model of the disease.

Published April 15 in the Journal of Neuroscience, the new research not only points to a new potential cause of Alzheimer's but also may eventually lead to a new treatment strategy.

"If indeed arginine consumption is so important to the disease process, maybe we could block it and reverse the disease," said senior author Carol Colton, professor of neurology at the Duke University School of Medicine, and a member of the Duke Institute for Brain Sciences.

The brains of people with Alzheimer's disease show two hallmarks -- 'plaques' and 'tangles' -- that researchers have puzzled over for some time. Plaques are the build up of sticky proteins called beta amyloid, and tangles are twisted strands of a protein called tau.

In the study, the scientists used a type of mouse, called CVN-AD, that they had created several years ago by swapping out a handful of important genes to make the animal's immune system more similar to a human's.

Compared with other mice used in Alzheimer's research, the CVN-AD mouse has it all: plaques and tangles, behavior changes, and neuron loss.

In addition, the gradual onset of these symptoms in the CVN-AD mouse gave researchers a chance to study its brain over time and to focus on how the disease begins, said the study's first author Matthew Kan, an MD/PhD student in Colton's lab.

Looking for immune abnormalities throughout the lifespan of the mice, the group found that most immune system components stayed the same in number, but a type of brain-resident immune cells called microglia that are known first responders to infection begin to divide and change early in the disease.

The microglia express a molecule, CD11c, on their surface. Isolating these cells and analyzing their patterns of gene activity, the scientists found heightened expression of genes associated with suppression of the immune system. They also found dampened expression of genes that work to ramp up the immune system.

"It's surprising, because [suppression of the immune system is] not what the field has been thinking is happening in AD," Kan said. Instead, scientists have previously assumed that the brain releases molecules involved in ramping up the immune system, that supposedly damage the brain.

The group did find CD11c microglia and arginase, an enzyme that breaks down arginine, are highly expressed in regions of the brain involved in memory, in the same regions where neurons had died.

Blocking arginase using the small drug difluoromethylornithine (DFMO) before the start of symptoms in the mice, the scientists saw fewer CD11c microglia and plaques develop in their brains. These mice performed better on memory tests.

"All of this suggests to us that if you can block this local process of amino acid deprivation, then you can protect -- the mouse, at least -- from Alzheimer's disease," Kan said.

DFMO is being investigated in human clinical trials to treat some types of cancer, but it hasn't been tested as a potential therapy for Alzheimer's. In the new study, Colton's group administered it before the onset of symptoms; now they are investigating whether DFMO can treat features of Alzheimer's after they appear.

Does the study suggest that people should eat more arginine or take dietary supplements? The answer is 'no,' Colton said, partly because a dense mesh of cells and blood vessels called the blood-brain barrier determines how much arginine will enter the brain. Eating more arginine may not help more get into the sites of the brain that need it. Besides, if the scientists' theory is correct, then the enzyme arginase, unless it's blocked, would still break down the arginine.

"We see this study opening the doors to thinking about Alzheimer's in a completely different way, to break the stalemate of ideas in AD," Colton said. "The field has been driven by amyloid for the past 15, 20 years and we have to look at other things because we still do not understand the mechanism of disease or how to develop effective therapeutics."

Epigenomics of Alzheimer's disease progression

Our susceptibility to disease depends both on the genes that we inherit from our parents and on our lifetime experiences. These two components -- nature and nurture -- seem to affect very different processes in the context of Alzheimer's disease, according to a new study published today in the journal Nature. The study was carried out by an interdisciplinary team at MIT and the Broad Institute, and was co-led by Li-Huei Tsai, the Picower Professor at MIT and director of the Picower Institute for Learning and Memory, and Manolis Kellis, a professor in MIT's Computer Science and Artificial Intelligence Laboratory (CSAIL). The researchers analyzed changes that occur in genes and in regions that regulate genes as Alzheimer's disease progresses, using a mouse model of Alzheimer's disease that Tsai's lab originally developed several years ago. The mice were engineered so that the gene for a protein called p25 can be overstimulated in the brain, which prompts the mice to develop symptoms very similar to Alzheimer's disease in humans. "These programmable mice allowed us to study, for the first time, the changes occurring during early stages of the disease, before symptoms even begin to appear," Tsai says. "We could then compare them to changes in later stages of the disease, when neurodegeneration and cognitive impairment are evident." Opposing changes The researchers profiled multiple chemical modifications, known as epigenetic marks, in the hippocampus of mice expressing too much p25 and compared them with control mice. These epigenetic marks reveal the activity of diverse genomic regions -- in particular, the regulatory control regions that control the expression of nearby genes. The researchers also directly profiled the levels of all genes. "We found two opposing signatures associated with disease progression that are consistent with the pathophysiology of Alzheimer's disease," says Elizabeta Gjoneska, joint first author of the paper and a postdoc at the Picower Institute. "Neuronal plasticity processes that are involved in learning and memory were dampened, and immune and inflammatory pathways were activated." The active regions specifically matched regions active in a type of immune cells known as microglia, which are responsible for clearing away infected or damaged cells. They also secrete chemicals that produce inflammation. "Our data suggest that microglia are heavily activated during Alzheimer's disease progression, although it is unknown exactly how they contribute to the disease," Tsai says. "These cells are important for normal brain function and share their key cell-surface markers, CD14, with macrophages that infiltrate the brain from elsewhere in the body during disease progression." Conserved epigenomic signatures The researchers then compared the results in mice with what is known about Alzheimer's disease in humans. They found that differences in gene levels in the Alzheimer's-like mouse brain matched differences previously seen in the brains of Alzheimer's patients, which prompted them to ask if the epigenetic signatures might also be conserved. The researchers found that this was the case -- specifically, the same regulatory regions that were active or repressed in mice showed the same patterns in humans. They also found that the regions with increased activity in the mouse model of Alzheimer's disease had immune functions in humans, and the regions that showed decreased activity had neural functions in humans. "Our results show that functional conservation between human and mouse is not restricted to protein-coding genes," says Andreas Pfenning, joint first author of the study and a postdoc at MIT. "This opens up the use of epigenomics methods in model organisms to study an inaccessible organ like the brain, and how it changes in response to activity or disease." Genetic variants cluster in immune pathways Previous studies of the genomes of Alzheimer's patients had identified common genetic variants associated with the disease, but scientists did not know how these DNA variants could contribute to the disease, since the majority of them are found outside of protein-coding regions. "Our conserved epigenomic maps allowed us to now place these noncoding genetic variants in the context of disease-relevant regulatory regions and interpret their contribution to the disease predisposition," Kellis says. "As inherited common genetic variants always precede disease onset, they are always indicative of causal roles, and thus can shed additional light on the epigenomic alterations." The researchers found that genetic variants associated with Alzheimer's disease were only associated with immune processes, and not with neural processes, indicating that genetic predisposition to Alzheimer's disease primarily affects the circuitry of immune processes, rather than neuronal processes. "Our results suggest that repression of neural pathways does not represent genetic predisposition, even though it is a hallmark of Alzheimer's," Tsai says. "Instead, it may occur as a consequence of environmental factors and aging, and result from interactions with the altered immune pathways." The researchers identified a small number of master regulators that target many of the regulatory regions that overlap Alzheimer's-associated genetic variants in humans. Among these, PU.1 targets a large number of altered regulatory regions, and the genetic region encoding PU.1 is associated with Alzheimer's disease, suggesting PU.1 as a potential therapeutic target. "The new focus on immune-cell types, and the specific regulators uncovered, provide new therapeutic avenues," Kellis says. "Moreover, the conservation of epigenomic signatures between mouse and human provides a platform upon which we can test such therapeutics and their effect on cognition, pathology, and the epigenomic signatures of Alzheimer's."

Lost memories might be able to be restored, suggests research into marine snail

 

For decades, most neuroscientists have believed that memories are stored at the synapses -- the connections between brain cells, or neurons -- which are destroyed by Alzheimer's disease. The new study provides evidence contradicting the idea that long-term memory is stored at synapses. "Long-term memory is not stored at the synapse," said David Glanzman, a senior author of the study, and a UCLA professor of integrative biology and physiology and of neurobiology. "That's a radical idea, but that's where the evidence leads. The nervous system appears to be able to regenerate lost synaptic connections. If you can restore the synaptic connections, the memory will come back. It won't be easy, but I believe it's possible." The findings were published recently in eLife. Glanzman's research team studies a type of marine snail called Aplysia to understand the animal's learning and memory. The Aplysia displays a defensive response to protect its gill from potential harm, and the researchers are especially interested in its withdrawal reflex and the sensory and motor neurons that produce it. They enhanced the snail's withdrawal reflex by giving it several mild electrical shocks on its tail. The enhancement lasts for days after a series of electrical shocks, which indicates the snail's long-term memory. Glanzman explained that the shock causes the hormone serotonin to be released in the snail's central nervous system. Long-term memory is a function of the growth of new synaptic connections caused by the serotonin, said Glanzman, a member of UCLA's Brain Research Institute. As long-term memories are formed, the brain creates new proteins that are involved in making new synapses. If that process is disrupted -- for example by a concussion or other injury -- the proteins may not be synthesized and long-term memories cannot form. (This is why people cannot remember what happened moments before a concussion.) "If you train an animal on a task, inhibit its ability to produce proteins immediately after training, and then test it 24 hours later, the animal doesn't remember the training," Glanzman said. "However, if you train an animal, wait 24 hours, and then inject a protein synthesis inhibitor in its brain, the animal shows perfectly good memory 24 hours later. In other words, once memories are formed, if you temporarily disrupt protein synthesis, it doesn't affect long-term memory. That's true in the Aplysia and in human's brains." (This explains why people's older memories typically survive following a concussion.) Glanzman's team found the same mechanism held true when studying the snail's neurons in a Petri dish. The researchers placed the sensory and motor neurons that mediate the snail's withdrawal reflex in a Petri dish, where the neurons re-formed the synaptic connections that existed when the neurons were inside the snail's body. When serotonin was added to the dish, new synaptic connections formed between the sensory and motor neurons. But if the addition of serotonin was immediately followed by the addition of a substance that inhibits protein synthesis, the new synaptic growth was blocked; long-term memory could not be formed. The researchers also wanted to understand whether synapses disappeared when memories did. To find out, they counted the number of synapses in the dish and then, 24 hours later, added a protein synthesis inhibitor. One day later, they re-counted the synapses. What they found was that new synapses had grown and the synaptic connections between the neurons had been strengthened; late treatment with the protein synthesis inhibitor did not disrupt the long-term memory. The phenomenon is extremely similar to what happens in the snail's nervous system during this type of simple learning, Glanzman said. Next, the scientists added serotonin to a Petri dish containing a sensory neuron and motor neuron, waited 24 hours, and then added another brief pulse of serotonin -- which served to remind the neurons of the original training -- and immediately afterward add the protein synthesis inhibitor. This time, they found that synaptic growth and memory were erased. When they re-counted the synapses, they found that the number had reset to the number before the training, Glanzman said. This suggests that the "reminder" pulse of serotonin triggered a new round of memory consolidation, and that inhibiting protein synthesis during this "reconsolidation" erased the memory in the neurons. If the prevailing wisdom were true -- that memories are stored in the synapses -- the researchers should have found that the lost synapses were the same ones that had grown in response to the serotonin. But that's not what happened: Instead, they found that some of the new synapses were still present and some were gone, and that some of the original ones were gone, too. Glanzman said there was no obvious pattern to which synapses stayed and which disappeared, which implied that memory is not stored in synapses. When the scientists repeated the experiment in the snail, and then gave the animal a modest number of tail shocks -- which do not produce long-term memory in a naive snail -- the memory they thought had been completely erased returned. This implies that synaptic connections that were lost were apparently restored. "That suggests that the memory is not in the synapses but somewhere else," Glanzman said. "We think it's in the nucleus of the neurons. We haven't proved that, though." Glanzman said the research could have significant implications for people with Alzheimer's disease. Specifically, just because the disease is known to destroy synapses in the brain doesn't mean that memories are destroyed. "As long as the neurons are still alive, the memory will still be there, which means you may be able to recover some of the lost memories in the early stages of Alzheimer's," he said. Glanzman added that in the later stages of the disease, neurons die, which likely means that the memories cannot be recovered. The cellular and molecular processes seem to be very similar between the marine snail and humans, even though the snail has approximately 20,000 neurons and humans have about 1 trillion. Neurons each have several thousand synapses. Glanzman used to believe that traumatic memories could be erased but he has changed his mind. He now believes that, because memories are stored in the nucleus, it may be much more difficult to modify them. He will continue to study how the marine snail's memories are restored and how synapses re-grow. Co-authors of the study include Shanping Chen, Diancai Cai and Kaycey Pearce, research associates in Glanzman's laboratory. The research was funded by the National Institutes of Health's National Institute of Neurological Disorders and Stroke, the National Institute of Mental Health and the National Science Foundation. Almost all the processes that are involved in memory in the snail also have been shown to be involved in memory in the brains of mammals, Glanzman said. In a 1997 study published in the journal Science, Glanzman and colleagues identified a cellular mechanism in the Aplysia that plays an important role in learning and memory. A protein called N-methyl D-aspartate, or NMDA, receptor enhances the strength of synaptic connections in the nervous system and plays a vital role in memory and in certain kinds of learning in the mammalian brain as well. Glanzman's demonstration that the NMDA receptor plays a critical role in learning in a simple animal like the marine snail was entirely unexpected at the time.

Improving memory by suppressing a molecule that links aging to Alzheimer's disease

 

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In a new study conducted by the Sagol Department of Neurobiology at the University of Haifa and published recently in the Journal of Neuroscience, researchers report that they've found a way to improve memory by manipulating a specific molecule that is known to function poorly in old age and is closely linked to Alzheimer's disease.

The researchers even succeeded, for the first time, in manipulating the molecule's operations without creating any cognitive impairment.

"We know that in Alzheimer's, this protein, known as PERK, doesn't function properly. Our success in manipulating its expression without causing any harm to the proper functioning of the brain paves the way for improving memory and perhaps even slowing the pathological development of diseases like Alzheimer's," said Prof. Kobi Rosenblum, who heads the lab in which the research was done.

Previous studies at the University of Haifa and other labs throughout the world had shown that the brain's process of formulating memory is linked to the synthesis of proteins; high rates of protein production will lead to a strong memory that is retained over the long term, while a slow rate of protein production leads to weak memories that are less likely to be impressed on a person's long-term memory and thus forgotten.

In the current study, the researchers, Dr. Hadile Ounallah-Saad and Dr. Vijendra Sharma, both of whom work in Prof. Rosenblum's lab at the Sagol Department of Neurobiology, sought to examine the activity of a protein called elF2 alpha, a protein that's known as the "spigot" or regulator that determines the pace of protein synthesis in the brain during memory formation.

From earlier studies the researchers knew that there are three main molecules that act on the protein and either make it work, or stop it from working. During the first stage they sought to determine the relative importance and the task of each one of the molecules that control the activity of efF2 alpha and as a result, the ability to create memories. After doing tests at the tissue and cell levels, the researchers discovered that the main molecule controlling the efF2 alpha's activity was the PERK molecule.

"The fact that we identified the PERK as the primary controller had particular significance," said Dr. Ounallah-Saad. "Firstly, of course, we had identified the dominant component. Secondly, from previous studies we already knew that in generative diseases like Alzheimer's, PERK performs deficiently. Third, PERK acts on various cells, including neurons, as a monitor and controller of metabolic stress. In other words, we found a molecule that has a major impact on the process of creating and formulating memory, and which we know performs deficiently in people with Alzheimer's disease."

During the second stage of the study, the researchers sought to examine whether they could manipulate this molecule in rats in a way that would improve memory. To do this they used two accepted methods, one using a drug called a small-molecule inhibitor and the other making a genetic change to the brain cells using a type of virus also used in gene therapy.

After paralyzing PERK's activity or reducing its expression through gene therapy (which was done with the help of Dr. Efrat Edry, of the University's Center for Gene Manipulation in the Brain), the researchers measured a 30% increase in the memory of either positive or negative experiences. The rats also demonstrated improved long-term memory and enhanced behavioral plasticity, becoming better able to "forget" a bad experience. In other words, on a behavioral level it was clear that manipulating PERK by either of two methods improved memory and cognitive abilities.

When the researchers examined the tissues on a cell and molecular level, the discovered that the steps they'd taken had indeed stopped the expression of PERK, which allowed the "spigot" -- the elF2 alpha protein -- to perform better and increase the pace of protein synthesis. Even more, there was a clear correlation between memory function and the degree to which PERK was suppressed; the more efficiently PERK was suppressed, the better the memory function.

But the researchers faced another problem. Previous studies that had manipulated PERK in general in genetically engineered animals led to fixated behavior. "The brain operates in a most sophisticated fashion, with each action closely linked to many other actions," said Dr. Ounallah-Saad. "In our study we succeeded in maintaining such control of the PERK that it didn't influence the retrieval of existing memories, or do anything other cognitive damage."

"With this study we proved that we are capable of strengthening the process of protein synthesis in the brain and of creating stronger memories that last a long time," said Prof. Rosenblum. "The moment we did this by manipulating a molecule that we know performs deficiently in people with Alzheimer's and is linked to the aging process, we have paved the way for the possible development of drugs that can slow the progress of incurable diseases like degenerative brain conditions, Alzheimer's chief among them."

Mining big data yields Alzheimer's discovery

 

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Scientists at The University of Manchester have used a new way of working to identify a new gene linked to neurodegenerative diseases such as Alzheimer's. The discovery fills in another piece of the jigsaw when it comes to identifying people most at risk of developing the condition.

Researcher David Ashbrook and colleagues from the UK and USA used two of the world's largest collections of scientific data to compare the genes in mice and humans. Using brain scans from the ENIGMA Consortium and genetic information from The Mouse Brain Library, he was able to identify a novel gene, MGST3 that regulates the size of the hippocampus in both mouse and human, which is linked to a group of neurodegenerative diseases. The study has just been published in the journal BMC Genomics.

David, who works in Dr Reinmar Hager's lab at the Faculty of Life Sciences, says: "There is already the 'reserve hypothesis' that a person with a bigger hippocampus will have more of it to lose before the symptoms of Alzheimer's are spotted. By using ENIGMA to look at hippocampus size in humans and the corresponding genes and then matching those with genes in mice from the BXD system held in the Mouse Brain Library database we could identify this specific gene that influences neurological diseases."

He continues: "Ultimately this could provide another biomarker in the toolkit for identifying those at greatest risk of developing diseases such as Alzheimer's."

Dr Hager, senior author of the study, says: "What is critical about this research is that we have not only been able to identify this specific gene but also the networks it uses to influence a disease like Alzheimer's. We believe this information will be incredibly useful for future studies looking at treatments and preventative measures."

The ENIGMA Consortium is led by Professor Paul Thompson based at the University of California, Los Angeles, and contains brain images and gene information from nearly 25,000 subjects. The Mouse Brain Library, established by Professor Robert Williams based at the University of Tennessee Health Science Center, contains data on over 10,000 brains and numerical data from just over 20,000 mice.

David explains why combining the information held by both databases is so useful: "The key advantage of working this way is that it is much easier to identify a genetic variant in mice as they live in such controlled environments. By taking the information from mice and comparing it to human gene information we can identify the same variant much more quickly."

And David thinks this way of working will be used more often in the future: "We are living in a big data world thanks to the likes of the Human Genome Project and post-genome technologies. A lot of that information is now widely shared so by mining what we already know we can learn so much more, advancing our knowledge of diseases and ultimately improving detection and treatment."

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Story Source:

The above story is based on materials provided by Manchester University. Note: Materials may be edited for content and length.

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Journal Reference:

1. David G Ashbrook, Robert W Williams, Lu Lu, Jason L Stein, Derrek P Hibar, Thomas E Nichols, Sarah E Medland, Paul M Thompson, Reinmar Hager. Joint genetic analysis of hippocampal size in mouse and human identifies a novel gene linked to neurodegenerative disease. BMC Genomics, 2014; 15 (1): 850 DOI: 10.1186/1471-2164-15-850

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  Alzheimer’s disease

Posted: 15 Aug 2014 02:05 PM PDT

Alanna Shaikh at TED2013, about six months after giving a powerful talk about Alzheimer’s disease and the three strategies she was putting in place in case she should ever get it. Photo: Ryan Lash/TED

Global health expert Alanna Shaikh gave an unexpected and moving talk at TEDGlobal 2012, called “How I’m preparing to get Alzheimer’s.” In it, she told the story of her father’s struggle with the disease, and outlined some strategies she’d devised in case dementia struck her later in life, too. The TED Blog was curious: How is her experiment going?

While most of Shaikh’s goals haven’t exactly gone as planned, in the process, she’s had a lightbulb moment about how to think about dementia—and learned to be a better person, to boot. Here, a conversation about the relationship between kindness and health, and living an enjoyable life in the present while planning for the future.

What have you been up to since your talk went live two years ago?

I talked about three things I was trying to do to prepare for Alzheimer’s: physically preparing by becoming stronger and more flexible, cultivating hobbies that would stick with me through the illness and trying to change who I am to be better and nicer. What really succeeded, weirdly enough, is I honestly think I am a better person. By deliberately choosing to be kind over and over again, it seems to now come naturally to me.

What were you like before?

Very judgmental and critical. I was committed to being a good person, but I wasn’t particularly worried about being a nice person. One of my friends in college told me that his favorite thing about me was I always had something bitchy to say about someone. This is someone who loves me—he meant it as a positive. I don’t think anybody who’s known me in the last couple of years would say that now. Dealing with my dad made me realize how much nice actually matters. And kindness. I had never really thought about what kindness and niceness have to do with each other.

I’ve never thought about that. What is the difference between nice and kind?

Being nice is not making a fuss and letting things happen to you. Not protesting. Whereas kindness is about deliberately giving the best of yourself, and deliberately looking for ways to find the positive in things. The example I give sometimes is this: the office building I used to work in didn’t have enough elevators. So if you wanted to leave the building at any time between 5 and 6pm, it was just packed—the elevator would stop on every floor, it would take forever and it was all sweaty. There were these people on the third floor, and they were always laughing and flirting and holding the elevator for each other, and you’d end up crammed in the corner for five minutes while you waited for them to stop saying goodbye to each other and hugging and whatever. At the beginning, I was like, “Those damned idiots on the third floor—why can’t they just take the stairs?” And then I started deliberately thinking, “No, these are young people enjoying life.” And so I started to think of them as the happy people on the third floor, and then realized that they are just thinking about their lives, not necessarily thinking too much about what it meant to be crammed into the elevator while they said goodbye. I started to try to take that approach to everything, to really look for the positive perspective.

Sounds like generosity of spirit, in a way.

I guess so. Because I’m an expat, I move a lot. So each new place you live is a chance to be the person you are right then. I realized that people who know me where I’m living now in Kyrgyzstan think of me as this very funny, positive, kind person. I love that. It doesn’t feel fake. I think I really am that person now, and I love that I was able to do that. It was the hardest thing for me, thinking, “I can pretend that I’m nice, but can I really become nice?”

Have you thought about kindness and its role in healing and health? Do you think it’s better for us to be kind?

I’ve never thought about that before, but I’m sure it is. For one thing, I think it takes a lot less emotional energy to be kind. Think of me getting off that elevator thinking about the happy people around me, versus me getting off that elevator being all, “Grrrr.” It has to be better for my heart. It has to be better not to get all that cortisol revved up inside of me.

Alanna’s father in a happy moment, long after his Alzheimer’s had set in. Photo: Alanna Shaikh

There’s also the question of kindness in the healing professions — the idea that patients are more likely to respond well to compassionate doctors and healers who touch their patients.

I think that’s probably true. In my day job, I’ve been part of a lot of different trainings for physicians, and one of the amazing things we’ve discovered is that the part physicians really love is the interpersonal skills, learning how to talk to their patients gently and kindly. We started including that in basically everything we teach, whether we’re teaching infection control or HIV care or breastfeeding support or whatever. The first component is always, “How do you talk to patients so they’ll listen?” The doctors absolutely love that, because it turns out they’ve been yearning to connect kindly; they just didn’t have the tools. That is the first thing they see results from: talking to their patients differently brings them different results as medical professionals. It seems to bring better outcomes. Often, doctors are afraid that if they are kind they’ll lose their authority, or patients won’t take them seriously, so it’s valuable to have an outsider validate the idea that you can be a respected professional and still be kind and generous to people, and that you don’t have to be stern and harsh to be an authority figure.

Are you still doing the same exercises that you discussed in the talk?

The hobbies didn’t work out as well as I wanted. It turns out I only like making origami boxes, but I really have no interest in making any other kind of origami—zebras or cranes or anything. Everybody who saw the TED Talk gave me origami stuff. I have four books, I have all this paper — and I just make a lot of origami boxes.

That’s probably fine from a cognitive perspective. At this point, I can have a piece of paper in my hands, and be watching TV and look down, and I’ve made a box. So clearly, this is being hardwired into me, and that’s good. That’s probably better than being able to make lots of different things, from a what-if-I-get dementia perspective. But I thought I was going to have this whole fleet of little animals, and it turns out that that’s not me. I can become kinder, but I can’t become a person who likes making origami.

The same thing happened with the knitting. I never made it past being able to knit a blob. I’ve done better with drawing, though. I still draw, and it’s really enjoyable. Connecting to that part of me has been great. And I’ve found myself also taking a lot of pictures, because drawing has me thinking visually. Photography’s not a particularly useful what-if-I-get-Alzheimer’s hobby, but it’s a sign that I’m thinking visually.

When you have Alzheimer’s, what happens when you go to take a picture? Your brain just doesn’t take in what’s on the screen?

At the very end, if you handed my dad a camera, he would’ve held it upside-down or sideways. He just wouldn’t have known what to do with it. But if you gave him a pencil, he could sign his name. My dad was a college professor in a state system, so if you gave him paperwork, he would fill it out, right up until the end. If he saw something that was obviously some sort of bureaucratic form, he’d scribble nonsense on all the lines. So he still knew what to do with a pencil. A pencil was comfortable. But a camera was alien.

What about exercise?

I’ve kept up with weightlifting. Not as regularly as I should, but often enough—I feel like I’m maintaining muscle mass. I’m still a strong and muscular person. And I stopped doing regular yoga, but I miss it, and I’m going back. I was on a very committed schedule, and then my yoga teacher moved, and I was like, “Oh, I’ll use videos,“ but it turned out I wouldn’t. Now I do the sun salutation every other morning, and that’s sort of the extent of it.

In your talk, you seemed pretty positive that you were going to get Alzheimer’s. But what are the statistics, really?

I kind of tune that out, because there are so many unknowns in terms of how exactly my father developed Alzheimer’s. I’m going to have genetic testing done next time I’m in the US long enough to get it. They can determine whether you have the gene that makes you much more susceptible to developing the disease. Basically, if you have the mutation for early-onset Alzheimer’s – -which is what my father had — it’s almost inevitable that you’ll get the disease. Beyond that, testing can’t tell you much.

Alanna Shaikh enjoying drawing with her son. Photo: Alanna Shaikh

Would it give you an idea of when onset would be?

No, they can’t do that yet.

How old was your father when he started developing symptoms?

In his early 50s.

That’s sobering.

Yeah. I mean, we didn’t know really what the symptoms meant at the time, but in retrospect, you can very clearly see the Alzheimer’s developing.

What were some of the symptoms?

For him, it was disinhibition. He just started acting weird. We thought maybe he had bipolar disorder, as he had some manic episodes, and he started telling dirty jokes he never told before. He started talking about his childhood in Pakistan and India, which he never talked about because it was really traumatic. Those are also things that can happen if you’re having a midlife crisis, so we didn’t recognize it as dementia. It’s not your classic pattern.

It turns out that for people who are highly intelligent, it doesn’t necessarily manifest in the same way, because they’re really good at compensating. They have enough excess cognitive capacity to make up for dropping and losing things, for example. If they’re forgetting words or names, they have the ability to develop mnemonics — that sort of thing.

Have you been doing work with Alzheimer’s since the talk? Did people start approaching you?

They did, and that was one greatest things about doing the talk. I’d really never thought about it before as anything beyond my personal story. I thought, if you’re going to give a TED Talk, you have to tell your best story—and this was my best story, maybe it’d be useful to someone else. It turned out it was really useful to others. I get emailed probably once a week from someone telling me that they saw the talk, and it helped them. That’s just the best feeling, because if you watch the talk, you’ll see it was really, really hard for me to give. It’s good to know that something that was that difficult for me was worth it.

I’ve also met with the Alzheimer’s Association of California about talking to people for them. I’ve been part of a group that’s working to increase attention to neurological disorders. I’ve been contacted by other people who want me to get involved in outreach. I’ve been thinking a lot about how I can get involved in Alzheimer’s advocacy.

But I’ve also been thinking bigger. It was interesting coming at this as an international development person, because all of the people I know in the professional international development sphere saw the talk, came back, and said, “You realize that you’re basically talking about disaster risk reduction. In a lot of ways, you’re talking about the same resilience that you want to build in a community. You’re talking about what do you do if you live in a place that tends to be hit by tornadoes.” So I started thinking more broadly about how to think about a future that isn’t the future you choose. How can you build a life that you’re living right now that prepares you for both the best possible future and the worst possible future? It’s a really, really big topic, and it might be the one I think about for the rest of my life. It’s created this lens for me to look at the world, and to think about the work I do with global health, and how that all comes together into this idea of how to have a good life in the present that also prepares a good life in the future.

Where will you take this idea?

I’m actually in the beginning stages of writing a book, and it’s one of the big themes. When you read the comments on my talk, a lot of people say, “How can you let the future affect your life like that?” “She’s given up, she’s making a mistake.” It was really interesting to me, because people seem to have this idea that your life now would be inherently terrible if you thought about your future too much as you live your daily life. But it seems like the “you” in the future is really going to regret that choice. The future Alanna is going to come back and slap me upside the head if I pretend that she doesn’t exist right now. It seems to be a surprising idea that you can live a good life now that prepares you for a good future. People think of it as a trade-off.

It seems your talk helped you evolve the work already you do into something much bigger.

Yes, I wasn’t expecting that. When I did the talk, I had really never considered Alzheimer’s in the context of global health, even though dementia and its effects on society are part of the global health discussion. My area of specialty is a lot more about primary health care and building health systems. So they were totally separate things in my world. It was almost like people had to point it out to me.

The disconnect between personal and professional was so strong that when people asked me to do advocacy for Alzheimer’s, I’d say no at first. My thought, even as someone who’s at risk, was that I’d rather that money be spent on vaccination for children or something that seems like it would help more people. But as time went on, connecting to so many people about aging and dementia and the future of the health system, I finally realized that there are many things that can be done to help people with dementia that help everyone. It’s not an either/or trade-off. If you help caregivers, then you’re helping moms with young babies and people taking care of the elderly. If you teach health care providers to treat people with kindness, that benefits everyone. Taking health care and the future seriously benefits everyone. There are ways to think about dementia that are not dementia-exclusive. And I don’t think I would ever have had any of those thoughts if it hadn’t been for all the conversations I’ve had since the TED Talk.

I actually wrote the talk at TEDIndia in 2009, while watching one of the speakers. I started thinking, “If I were going to give a TED Talk, what would I say? What about me is interesting?” I realized I was actually doing this thing that’s fairly interesting. And so I wrote down the title, “How I’m Preparing to Get Alzheimer’s,” and then I wrote the entire TED Talk, sitting right there in the audience. I started crying as I wrote everything down.

And what happened with your father?

My dad died about two months after the talk. It’s hard, because people do always ask after my dad, and I have to tell them that. But he saw the talk, and I am glad. I don’t know how much he understood, but he knew it was me on a big stage talking to people — and he was proud of me, and that made him happy.

 

A New Idea for Treating Alzheimer’s

 

By Gary Stix | September 28, 2014

The views expressed are those of the author and are not necessarily those of Scientific American.

 

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If it’s good for the heart, it could also be good for the neurons, astrocytes and oligodendrocytes, cells that make up the main items on the brain’s parts list.

The heart-brain adage comes from epidemiological studies that show that people with cardiovascular risk factors such as high-blood pressure and elevated cholesterol levels, may be more at risk for Alzheimer’s and other dementias.

This connection between heart and brain has also led to some disappointments: clinical trials of lipid-lowering statins have not helped patients diagnosed with Alzheimer’s, although epidemiological studies suggest that long-term use of the drugs may help prevent Alzheimer’s and other dementias.

The link between head and heart is still being pursued because new Alzheimer’s drugs have failed time and again. One  approach that is now drawing some interest looks at the set of proteins that carry around fats in the brain. These lipoproteins could potentially act as molecular sponges that mop up the amyloid-beta peptide that clogs up connections among brain cells in Alzheimer’s.

One of these proteins—Apolipoprotein J, also known as clusterin—intrigues researchers because of the way it interacts with amyloid-beta and the status of its gene as a risk factor for Alzheimer’s.

A researcher from the University of Minnesota, Ling Li, recently presented preliminary work at the Alzheimer’s Drug Discovery Foundation annual meeting that showed that, at least in a lab dish, a molecule made up of a group of amino acids from APOJ is capable of protecting against the toxicity of the amyloid-beta peptide. It also quelled inflammation and promoted the health of synapses—the junctions where one brain cell encounters another. Earlier work by another group showed that the  peptide prevented the development of  lesions in the blood vessels of animals.

Li’s research will still require crossing a number of conceptual barriers to prove that an APOJ-derived drug can actually work in humans.  APOJ plays different roles in Alzheimer’s. In the healthy brain, it may help preserve the normal workings of brain cells, but it may also promote the Alzheimer’s disease process under other conditions.

From the preliminary results, Li hopes that the APOJ-derived peptide will  harness the beneficial effects of the protein. The work is still in early stages and Li and her team now plan to go on to test the peptide in mice. “The long term goal would be to find something that prevents or treats Alzheimer’s,” she says. An APOJ protein fragment—or a variety of other new ideas for drug candidates—are badly needed for a disease that affects tens of millions of people worldwide yet lacks any good treatment.

Image Source: Eliza Fitzhugh/Flickr-Creative Commons

2 Grown-Up Beverages That Keep Your Mind Young

 

Helpful people found this helpful.

These two adult beverages -- one that wakes people up in the morning and another that relaxes them in the evening -- may help keep the mind young: coffee and red wine.

According to research, these two beverages -- if enjoyed in moderation -- might help prevent the onset of Alzheimer's disease.

Staying Sharp
The news is no reason to start a coffee or wine habit. But if they're already part of your beverage repertoire, you might be interested to know that both seem to contain ingredients that could help ward off dementia. Animal studies show that something in coffee may help trigger the release of a special growth factor -- granulocyte colony-stimulating factor (GCSF) -- that recruits cells from bone marrow to help sweep out beta-amyloid deposits. (Those are the pesky plaques that cause Alzheimer's symptoms.) And the polyphenols in red wine may have similar benefits, reducing levels of peptides that contribute to Alzheimer's plaques. (Do you forget things simply because you're distracted? Find out what the symptoms of adult ADHD are.)

Very Stimulating
The substances in coffee and wine may also help strengthen the brain, either by helping it forge new connections or protecting it from the neurotoxic effects of Alzheimer's plaques. Ready for a younger, sharper mind? Try these rules for the road if you're a coffee or red wine drinker:

• Make it fully leaded. In studies, decaf coffee didn't provide the same benefits. Of course, if you're caffeine sensitive, coffee probably isn't for you at all. (Could coffee help you dodge diabetes?)
• Enjoy responsibly. Heavy or binge drinking -- even with polyphenol-rich red wine -- is linked to worse cognitive performance. Limit yourself to one drink a day if you're a woman, or one to two drinks a day if you're a man. (Not a drinker? Try this heart-healthy wine substitute.)

Age Benefits

Enjoying coffee if you like it -- and it likes you -- can make your RealAge 0.3 years younger.

August, 2011