1. Study sheds light on link between diseases like Alzheimer’s and normal aging in the brain

    May 27, 2017 by Ashley

    From the Frontiers press release:

    In a recent Frontiers in Aging Neuroscience paper, Drs. Della David and Frank Baumann together with their teams at the German Center for Neurodegenerative Diseases and Hertie Institute, showed that changes in proteins associated with aging were directly implicated in the protein formations commonly associated with Alzheimer’s disease.

    Neurodegenerative diseases are often associated with protein aggregates. These are clumps of proteins created when misfolded proteins — proteins that have lost the elaborate but recognizable shape that dictates their function — assemble together to form a highly intractable structure. Recent research has also shown that even in the absence of disease, proteins can aggregate increasingly with age.

    In the case of Alzheimer’s the researchers investigated whether the Amyloid beta (A?) aggregates closely associated with the disease could be induced by aging seeds: proteins that clump together with age to form aggregates. This would occur through a hypothesized phenomenon called cross-seeding, where different protein aggregates can induce each other’s aggregation. Crucially, the few existing examples of cross-seeding occur between disease-associated proteins.

    The study’s experiments on C. elegans, an organism whose limited number of cells and relative complexity makes it an ideal test subject, showed that age-dependent protein aggregates can induce A? aggregation in vitro, and that the age-dependent protein aggregates of older C. elegans specimens were particularly likely to cross-seed A? aggregates.

    In order to verify the applicability of these results to mammals, the same tests were performed in vitro on mouse brain extracts of varying age, with similar outcomes.

    By performing a protein count via mass spectrometry for C. elegans, the study also identified some proteins for further investigation. The most promising candidates for cross-seeding activity were proteins present as minor components in disease-associated aggregates, which aggregate increasingly after middle-age.

    Furthermore, the researchers demonstrated that one of these aggregation-prone proteins, PAR-5, can induce A? toxicity in vivo. According to paralysis rates, the combination of overexpressed PAR-5 with overexpressed A? accelerated A? toxicity in C. elegans.

    Combined with the mass spectrometry, these experiments further highlight that certain minor components may qualify as proteins that “could be more prone to aggregate in specific brain regions and thus help the generation and spreading of disease-associated seeds in certain brain circuits.”

    This study thus predicts that changes in protein conformations associated with old age may initiate Alzheimer’s disease through A? aggregation and toxicity.

    Given that the study’s in vitro assays cannot mimic the entire complexity of the brain and picture all neurobiological interactions, the researchers encourage an “in vivo assessment by injecting age-dependent aggregates into a pre-symptomatic transgenic mouse models for Alzheimer’s disease.”

    They add that aggregating proteins should be mapped in both healthy and neurodegenerative human brain samples, as a way of clarifying “which aging seeds need to be looked at and whether certain aging seeds would be more prone to seed or associate with specific disease types in specific anatomical areas.”


  2. Exercising can protect the brain from Alzheimer’s disease

    May 26, 2017 by Ashley

    From the University of British Columbia Okanagan campus press release:

    The evidence is clear. Physical activity is associated with a reduced risk of Alzheimer’s disease, says a panel of researchers and not-for-profit leaders, led by UBC’s Okanagan campus.

    The researchers also confirmed that regular physical activity may improve the performance of daily activities for people afflicted with Alzheimer’s. Their conclusions may have significant implications for the 1.1 million Canadians affected directly or indirectly by dementia.

    “As there is no current cure for Alzheimer’s, there is an urgent need for interventions to reduce the risk of developing it and to help manage the symptoms,” says study first author Kathleen Martin Ginis, professor in UBC Okanagan’s School of Health and Exercise Sciences. “After evaluating all the research available, our panel agrees that physical activity is a practical, economical and accessible intervention for both the prevention and management of Alzheimer’s disease and other dementias.”

    Martin Ginis and her cohort reviewed data from more than 150 research articles about the impact of physical activity on people with Alzheimer’s. Some of the work explored how physical activity improves the patient’s quality of life and the others examined the risk of developing Alzheimer’s based on the amount of activity in which an individual participated.

    The panel concluded that regular physical activity improves activities of daily living and mobility in in older adults with Alzheimer’s and may improve general cognition and balance. They also established that older adults not diagnosed with Alzheimer’s who are physically active, were significantly less likely to develop the disease compared to people who were inactive.

    “This is exciting work,” says Martin Ginis. “From here we were able to prepare a consensus statement and messaging which not only has community backing, but is also evidence-based. Now we have the tool to promote the protective benefit of physical activity to older adults. I’m hopeful this will move the needle on this major health concern.”

    Alzheimer’s disease is the most common form of dementia, characterized by progressive neurodegeneration that results in severe cognitive impairment, compromised physical ability and loss of independence. The number of worldwide cases is expected to increase from 30.8 million in 2010 to more than 106 million in 2050.


  3. Spread of tau protein measured in brains of Alzheimer’s patients

    May 25, 2017 by Ashley

    From the Karolinska Institutet press release:

    In a new study presented in Molecular Psychiatry, researchers at Karolinska Institutet have measured how deposits of the pathological protein tau spread through the brain over the course of Alzheimer’s disease. Their results show that the size of the deposit and the speed of its spread differ from one individual to the next, and that large amounts of tau in the brain can be linked to episodic memory impairment.

    Already in a very early phase of Alzheimer’s disease there is an accumulation of tau in the brain cells, where its adverse effect on cell function causes memory impairment. It is therefore an attractive target for vaccine researchers. For the present study, Professor Agneta Nordberg at Karolinska Institutet’s Department of Neurobiology, Care Sciences and Society and her doctoral student Konstantinos Chiotis along with the rest of her team used PET brain imaging to measure the spread of tau deposits as well as the amyloid plaque associated with Alzheimer’s disease, and charted the energy metabolism of the brain cells. They then examined how these three parameters changed over the course of the disease.

    “There’s been an international race to measure tau spread, and we probably got there first,” says Professor Nordberg. “There are no previous reports on how tau deposits spread after 17 months into the disease. Our results can improve understanding of tau accumulation in Alzheimer’s disease, help ongoing research to quantify the effect of tau vaccines, and enable early diagnosis.”

    The study included 16 patients at different stages of Alzheimer’s disease from the memory unit at Karolinska Hospital in Huddinge. The patients were given a series of neurological memory tests and underwent PET scans at 17-month intervals. While all 16 participants had abundant amyloid plaque deposition in the brain, the size and speed of spread of their tau deposits differed significantly between individuals.

    “We also saw a strong direct correlation between size of deposit and episodic memory impairment,” continues Professor Nordberg. “This could explain why the disease progresses at such a varying rate from one patient to the other. That said, tau doesn’t seem to have much of an effect on the global general memory, which is more reasonably related to brain metabolism.”

    The study was conducted in collaboration with Uppsala University, where the PET scans were performed.


  4. Study measures communication in couples affected by dementia

    May 20, 2017 by Ashley

    From the Florida Atlantic University press release:

    In marriage, good communication is key to a fulfilling and enduring relationship. For people with dementia, communicating needs, emotions and interacting with others becomes increasingly difficult as communication deteriorates as dementia progresses. Problems in communicating lead to misinterpretations and misunderstandings, which often cause considerable stress for family members, especially the spouse caregivers as well as the patient.

    But all is not lost according to the first study to look at and measure communication outcomes in both the caregiver spouse and the patient with dementia. In fact, researchers from Florida Atlantic University have found that “practice makes perfect” with the right intervention and a tool that can accurately measure couples’ communication. Results from the study are published in the journal Issues in Mental Health Nursing.

    “There has been very little focus on the patient with dementia’s role in maintaining spousal relationships through conversation,” said Christine L. Williams, DNSc, principal investigator of the study and a professor and director of the Ph.D. in Nursing Program in FAU’s Christine E. Lynn College of Nursing, who designed the intervention program and developed the first tool that measures couples’ communication. “Maybe it’s because researchers assume that the patient can’t have a positive influence on communication because of dementia. We wanted to explore this issue further, especially for couples with a history of special memories shared over decades of marriage.”

    For the study, Williams videotaped and later analyzed and measured 118 conversations between 15 patients with varying degrees of dementia and their spouses — married an average of 45 years — to evaluate the effects of a 10-week communication-enhancement intervention on participant’s communication and mental health.

    Caregivers were taught to communicate in a manner that was clear, succinct and respectful, and to avoid testing memory and arguing. Spouses with dementia were given the opportunity to practice their conversation skills with a member of the research team who was trained in communication deficits associated with dementia as well as the intervention. Conversations were recorded at the couples’ homes. After setting up the video camera, Williams conducted the intervention and then left the room for 10 minutes. Couples were instructed to converse on a topic of their choice for 10 minutes.

    “There are very few studies that have looked at actual communication between couples in these circumstances and tried to analyze it,” said Williams. “For instance, I’ve seen studies where they have taught communication strategies to caregivers, but then what they measure is the caregivers’ knowledge about communication, which doesn’t tell you anything about whether or not they were able to communicate.”

    Unlike other measures of patient communication, the Verbal and Nonverbal Interaction Scale-CR (VNIS-CR) tool developed by Williams takes into account nonverbal behaviors, which account for more than 70 percent of communication, as well as verbal behaviors. VNIS-CR delineates social and unsociable behaviors, characterizes patient behaviors (not through the lens of a caregiver), and is targeted to spousal relationships in the home. Consisting of 13 social and 13 unsociable communication behaviors with both verbal and nonverbal items, the tool helps to describe sociable and unsociable communication in patients with dementia as they engage in conversations with their spouses.

    Nonverbal, non-sociable items in the tool included aloofness, staring into space and being nonresponsive; nonverbal, sociable items included looking or gazing at the spouse, being affectionate and joking. Social verbal behaviors included using coherent conversation, responding to questions, and addressing their partner by name or endearment. Unsociable verbal behaviors included shouting, cursing and unintelligible communication. The 13-item scores were summed up to obtain the final score.

    “Using this new tool, I was able to confirm that the intervention I used actually worked and that communication improved in both the spouse caregiver and the patient over time,” said Williams. “I was ecstatic because I originally thought that maybe the caregiver’s communication would improve and that would be great. However, to have positive changes in a person who is continuing to decline over 10 weeks, which is a long time, was something I really did not expect. This intervention worked for both the caregiver and the patient and we now have a tool to demonstrate it.”

    Globally, Alzheimer’s disease (AD) and related dementias affected 35.6 million individuals in 2010 and it is expected to grow to 115.4 million by 2050. The prevalence of dementia will increase as longevity increases and future family caregivers are likely to be predominantly spouses. In the United States, most people with dementia are cared for by their spouses.

    “As patients progress with dementia, couples don’t have to lose everything especially if they are engaged, if they can still relate to one another and if they focus on the here and now,” said Williams.

    The VNIS-CR could be used in clinical practice to describe changes in social communication abilities over time, as well as to educate spousal caregivers about the importance of encouraging sociable communication. Knowledge gained from using this tool could better guide the development of interventions to support intimate relationships and ultimately measure changes following those interventions.


  5. New hope for patients with primary progressive aphasia

    May 18, 2017 by Ashley

    From the Baycrest Centre for Geriatric Care press release:

    A Baycrest Health Sciences researcher and clinician has developed the first group language intervention that helps individuals losing the ability to speak due to a rare form of dementia, and could help patients maintain their communication abilities for longer.

    Primary Progressive Aphasia (PPA) is a unique language disorder that involves struggles with incorrect word substitutions, mispronounced words and/or difficulty understanding simple words and forgetting names of familiar objects and people. With PPA, language function declines before the memory systems, which is the opposite of Alzheimer’s disease.

    Dr. Regina Jokel, a speech-language pathologist at Baycrest’s Sam and Ida Ross Memory Clinic and a clinician-scientist with the Rotman Research Institute (RRI), has developed the first structured group intervention for PPA patients and their caregivers. This intervention could also help treat patients with other communication problems, such as mild cognitive impairment (a condition that is likely to develop into Alzheimer’s). The results of her pilot program were published in the Journal of Communication Disorders on April 14, 2017.

    “This research aims to address the needs of one of the most underserviced populations in language disorders,” says Dr. Jokel. “Individuals with PPA are often referred to either Alzheimer’s programs or aphasia centres. Neither option is appropriate in this case, which often leaves individuals with PPA adrift in our health care system. Our group intervention has the potential to fill the existing void and reduce demands on numerous other health services.”

    Language rehabilitation has made headway in managing the disorder, but there are limited PPA treatment options, adds Dr. Jokel.

    Dr. Jokel is one of the few researchers in the world studying this disease. She was motivated to acquire her PhD. and devise the intervention after encountering her first PPA patient more than 25 years ago.

    “When I realized the patient had PPA, I ran to the rehabilitation literature thinking that he needed to start some sort of therapy. I ran a search and came up with nothing. Absolutely nothing,” says Jokel. “That’s when I thought, ‘It’s time to design something.'”

    The 10-week intervention included working on language activities, learning communication strategies and receiving counselling and education for both patients and their caregivers. During the pilot program, patients either improved or remained unchanged on communication assessments for adults with communication disorders. Their caregivers also reported being better prepared to manage psychosocial issues and communication challenges and had more knowledge of PPA and the disease’s progression.

    “In progressive disorders, any sign of maintaining current level of function should be interpreted as success,” says Dr. Jokel. “Slowing the progression and maintenance of communication abilities should be the most important goal.”

    For the study’s next steps, Dr. Jokel has received support from a Brain Canada-Alzheimer’s Association partnership grant to assess the therapy’s impact on the language skills of PPA patients. With support from the Ontario Brain Institute, she is also collaborating with RRI brain rehabilitation scientist, Dr. Jed Meltzer, to explore the effect of brain stimulation on patients also undergoing language therapy.


  6. Study suggests Alzheimer’s disease likely not caused by low body mass index

    May 17, 2017 by Ashley

    From the Endocrine Society press release:

    A new large-scale genetic study found that low body mass index (BMI) is likely not a causal risk factor for Alzheimer’s disease, as earlier research had suggested, according to a study published in the Endocrine Society’s Journal of Clinical Endocrinology & Metabolism.

    “Although prior studies found an association between Alzheimer’s disease and low BMI, the new findings suggest this is not a causal relationship,” said the study’s senior author, Ruth Frikke-Schmidt, M.D., D.M.Sc., Ph.D., Chief Physician at Rigshospitalet in Copenhagen, Denmark, and Associate Research Professor at the University of Copenhagen. “The association can likely be explained by the fact that individuals with Alzheimer’s disease are more likely to have low BMIs due to loss of appetite and weight loss in the early stages of the disease.”

    More than 5 million Americans have Alzheimer’s disease, according to the Alzheimer’s Association’s 2017 Alzheimer’s Disease Facts and Figures Report. The disease affects the brain and is a common form of dementia. It is the sixth leading cause of death in the United States.

    To examine the association between Alzheimer’s disease and low BMI, the researchers analyzed blood and DNA samples from 95,578 participants in the Copenhagen General Population Study (CGPS). Of the participants, 645 individuals developed Alzheimer’s disease.

    The researchers analyzed the study participants’ DNA for the presence of five genetic variants that have strong associations with BMI. Based on how many variants were found, participants were divided into four groups to reflect the likelihood of low BMI. The researchers also analyzed data from up to 249,796 individuals participating in the Genetic Investigation of ANthropometric Traits (GIANT) consortium for the genetic variants closely linked to low BMI.

    The analysis found the presence of the genetic variants tied to low BMI was not associated with increased risk of Alzheimer’s disease. For comparison, the researchers examined if individuals with genetic variants connected to high BMI were more likely to have type 2 diabetes and did find the expected causal relationship.

    “We found individuals with lifelong low BMI due to genetic variation were not at increased risk of Alzheimer’s disease,” Frikke-Schmidt said. “Since genetic variants are not affected by other risk factors or diseases, this is a clean measure that can help to determine causality. The findings highlight that testing causality of a risk factor is pivotal before considering changing public health recommendations based on observational data alone.”


  7. Shortage of progranulin is a frequent cause of frontotemporal dementia

    May 15, 2017 by Ashley

    From the VIB (the Flanders Institute for Biotechnology) press release:

    In a recent study in Human Molecular Genetics, researchers from VIB and KU Leuven led by prof. Philip Van Damme, reveal a novel function for progranulin in lysosomes: it acts as chaperone of the lysosomal protease cathepsin D. The results were obtained in collaboration with Prof. Paul Saftig from the University of Kiel.

    Prof. Philip Van Damme (VIB-KU Leuven/University Hospital Leuven): “Our findings suggest that dysfunction of lysosomal enzymes such as cathepsin D can contribute to neuronal dysfunction caused by progranulin deficiency in diseases such as frontotemporal dementia. These are important new insights in our search for solutions.”

    Frontotemporal dementia

    Frontotemporal dementia or FTD is the second most common form of early onset dementia, after Alzheimer’s Disease, characterized by neuronal loss in the frontal and anterior temporal lobes. It generally affects people in their mid 40’s to mid 60’s leading to severe changes in behavior or language problems. Behavioral changes include, but are not limited to, apathy and disinhibition, which eventually prohibit the patient’s ability for normal social interaction. Patients can also display different language problems leading to semantic dementia or primary progressive aphasia. Currently, there is no treatment available for this disease, limiting the prognosis of FTD patients to 6-8 years after symptom onset.

    In almost half of the patients, the disease runs in the family. Mutations in the gene encoding progranulin are one of the most frequent causes and result in a 50% loss of functional progranulin protein. Efforts to model the human disease in mice have been disappointing as the full knockout of progranulin leads to a mild phenotype without neurodegeneration.

    Progranulin functions as a neurotrophic factor in vivo

    Previous studies have shown that progranulin can stimulate neuronal survival and neurite outgrowth in cultures. These findings led to the hypothesis that neurodegeneration in FTD patients might occur due to a reduced trophic support for neurons.

    An in vivo paradigm of facial nerve crush injury was used to study the neurotrophic effects of progranulin in more detail. The recovery from such injury was delayed in the absence of progranulin and reintroduction of human progranulin in these mice could completely rescue this deficit, indicating that axonal regeneration after nerve injury depends specifically on the presence of progranulin. Using newly generated microglial and neuronal specific progranulin knockout mice, it was show that basal progranulin expression is mainly neuronal and that only neuronal progranulin deletion drives the axonal outgrowth deficit.

    Progranulin acts as a chaperone for cathepsin D to stabilize the enzyme and increase its proteolytic capacity

    A transcriptomics approach to identify possible mediators of the observed effects pointed towards the lysosomal aspartic protease cathepsin d (CTSD) as the most upregulated gene in progranulin knockout mice. A direct interaction between the two proteins was established. In the brains of aged progranulin knockout mice, the relative CTSD activity was reduced. By adding progranulin, the proteolytic activity of CTSD could be stimulated in a dose-dependent manner. Progranulin was shown to bind to CTSD and prevented its heat induced degradation. The interaction between GRN and CTSD proved to be necessary for the recovery after facial nerve injury, linking the neurotrophic effects of GRN to a lysosomal chaperone function on CTSD.


  8. PTSD, certain prescriptions for PTSD may raise risk for dementia

    by Ashley

    From the American Geriatrics Society press release:

    Researchers are discovering that post-traumatic stress disorder (PTSD) is a significant risk factor in developing dementia. Dementia is a memory problem that affects a person’s ability to carry out usual tasks. Dementia is a leading cause of serious illness, disability, and death. It often requires care in a nursing home or other long-term care facility for people aged 65 and older.

    Until now, researchers didn’t know whether the kinds of medications used for people with PTSD could increase risks for dementia. (These medications include including antidepressants, antipsychotics, sedatives, or tranquilizers.) A new study, published in the Journal of the American Geriatrics Society, examined this connection.

    In their study, researchers examined information from 3,139,780 veterans aged 56 and older. At the beginning of the study, in 2003, the veterans were receiving health care from a Veterans Health Administration facility. Almost all the veterans were male and 82% were white.

    Of the veterans in the study, 5.4% had been diagnosed with PTSD. As the researchers looked at the data over the study’s nine-year follow-up period, they also included veterans who were diagnosed with dementia.

    Research has previously shown that veterans with PTSD are more likely to have health problems linked to a higher risk for dementia. These include traumatic brain injury, diabetes, chronic obstructive pulmonary disease (COPD), psychiatric disorders, substance abuse, and other health issues.

    In this study, researchers discovered that taking certain antidepressants, tranquilizers, sedatives, or antipsychotic medications significantly increased veterans’ risks for developing dementia compared to the risks for veterans who didn’t take such medications.

    Medicines that significantly increased dementia risk included:

    • Selective serotonin reuptake inhibitors (SSRIs)
    • Novel antidepressants
    • Atypical antipsychotics

    The increase in the risk of dementia for veterans taking the drugs was the same whether or not they were diagnosed with PTSD. (This is compared to veterans who weren’t taking these drugs.)

    What’s more, veterans who used three classes of medications were also more likely to be diagnosed with dementia whether or not they had PTSD. These medicines include:

    • Novel antidepressants
    • Serotonin-norepinephrine reuptake inhibitors (SNRIs)
    • Benzodiazepines

    The researchers noted that an interaction among these “psychoactive” drugs could potentially affect how PTSD impacts a person’s risk for developing dementia. The researchers concluded that further research should be conducted to learn more about PTSD and psychoactive drugs, including dosage, how long to take the medications, and which people could most benefit from them.


  9. Study suggests cannabis reverses aging processes in the brain

    May 13, 2017 by Ashley

    From the University of Bonn press release:

    Memory performance decreases with increasing age. Cannabis can reverse these ageing processes in the brain. This was shown in mice by scientists at the University of Bonn with their colleagues at The Hebrew University of Jerusalem (Israel). Old animals were able to regress to the state of two-month-old mice with a prolonged low-dose treatment with a cannabis active ingredient. This opens up new options, for instance, when it comes to treating dementia. The results are now presented in the journal Nature Medicine.

    Like any other organ, our brain ages. As a result, cognitive ability also decreases with increasing age. This can be noticed, for instance, in that it becomes more difficult to learn new things or devote attention to several things at the same time. This process is normal, but can also promote dementia. Researchers have long been looking for ways to slow down or even reverse this process.

    Scientists at the University of Bonn and The Hebrew University of Jerusalem (Israel) have now achieved this in mice. These animals have a relatively short life expectancy in nature and display pronounced cognitive deficits even at twelve months of age. The researchers administered a small quantity of THC, the active ingredient in the hemp plant (cannabis), to mice aged two, twelve and 18 months over a period of four weeks.

    Afterwards, they tested learning capacity and memory performance in the animals — including, for instance, orientation skills and the recognition of other mice. Mice who were only given a placebo displayed natural age-dependent learning and memory losses. In contrast, the cognitive functions of the animals treated with cannabis were just as good as the two-month-old control animals. “The treatment completely reversed the loss of performance in the old animals,” reported Prof. Andreas Zimmer from the Institute of Molecular Psychiatry at the University of Bonn and member of the Cluster of Excellence ImmunoSensation.

    Years of meticulous research

    This treatment success is the result of years of meticulous research. First of all, the scientists discovered that the brain ages much faster when mice do not possess any functional receptors for THC. These cannabinoid 1 (CB1) receptors are proteins to which the substances dock and thus trigger a signal chain. CB1 is also the reason for the intoxicating effect of THC in cannabis products, such as hashish or marihuana, which accumulate at the receptor. THC imitates the effect of cannabinoids produced naturally in the body, which fulfil important functions in the brain. “With increasing age, the quantity of the cannabinoids naturally formed in the brain reduces,” says Prof. Zimmer. “When the activity of the cannabinoid system declines, we find rapid ageing in the brain.”

    To discover precisely what effect the THC treatment has in old mice, the researchers examined the brain tissue and gene activity of the treated mice. The findings were surprising: the molecular signature no longer corresponded to that of old animals, but was instead very similar to that of young animals. The number of links between the nerve cells in the brain also increased again, which is an important prerequisite for learning ability. “It looked as though the THC treatment turned back the molecular clock,” says Zimmer.

    Next step: clinical trial on humans

    A low dose of the administered THC was chosen so that there was no intoxicating effect in the mice. Cannabis products are already permitted as medications, for instance as pain relief. As a next step, the researchers want to conduct a clinical trial to investigate whether THC also reverses ageing processes in the brain in humans and can increase cognitive ability.

    The North Rhine-Westphalia science minister Svenja Schulze appeared thrilled by the study: “The promotion of knowledge-led research is indispensable, as it is the breeding ground for all matters relating to application. Although there is a long path from mice to humans, I feel extremely positive about the prospect that THC could be used to treat dementia, for instance.”


  10. Gene mutation may speed up memory loss in Alzheimer’s disease

    May 12, 2017 by Ashley

    From the American Academy of Neurology (AAN) press release:

    A gene mutation may accelerate the loss of memory and thinking skills in people who are at risk for Alzheimer’s disease, according to a study published in the May 3, 2017, online issue of Neurology®, the medical journal of the American Academy of Neurology. The gene mutation is called the BDNF Val66Met allele, or just the Met allele.

    Brain derived neurotrophic factor (BDNF) is a protein produced by the gene of the same name. It is one of a group of proteins called neurotrophins that help nerve cells grow, specialize and survive. Alleles are parts of genes that work in pairs on the chromosomes to determine a person’s traits.

    “We found that people with Alzheimer’s risk who have this BDNF gene mutation called the Met allele may have a more rapid decline of memory and thinking skills,” said study author Ozioma Okonkwo, PhD, of the University of Wisconsin School of Medicine in Madison, Wisc. “Because this gene can be detected before the symptoms of Alzheimer’s start, and because this presymptomatic phase is thought to be a critical period for treatments that could delay or prevent the disease, it could be a great target for early treatments.”

    For the study, researchers followed 1,023 people with an average age of 55 for up to 13 years who were at risk for Alzheimer’s disease but at the start were still healthy. Participants gave blood samples which were tested for the Met allele gene mutation. Their memory and thinking skills were evaluated at the start of the study and at each study visit, up to five visits. Of that group, 140 were also tested with neuroimaging for beta-amyloid, a sticky protein that can build up into plaques found in the brains of people with Alzheimer’s disease.

    A total of 32 percent of the participants had the Met allele. Researchers found that when compared to people without the gene mutation, those with the mutation lost memory and thinking skills more rapidly. On tests of verbal learning and memory, those with no gene mutation improved by 0.002 units per year, while the scores of people with the mutation declined by 0.021 units per year.

    The researchers also found that people with the gene mutation who also had more beta-amyloid had an even steeper rate of decline.

    “When there is no mutation, it is possible the BDNF gene and the protein it produces are better able to be protective, thereby preserving memory and thinking skills,” Okonkwo said. “This is especially interesting because previous studies have shown that exercise can increase levels of BDNF. It is critical for future studies to further investigate the role that the BDNF gene and protein have in beta-amyloid accumulation in the brain.”

    A major strength of the study is that it was one of the largest studies investigating this mutation. A limitation is that the study participants were predominantly white. Also, the number of people with beta-amyloid data was limited.