1. Study suggests body clock disruptions occur years before memory loss in Alzheimer’s

    February 15, 2018 by Ashley

    From the Washington University in St. Louis press release:

    People with Alzheimer’s disease are known to have disturbances in their internal body clocks that affect the sleep/wake cycle and may increase risk of developing the disorder. Now, new research at Washington University School of Medicine in St. Louis indicates that such circadian rhythm disruptions also occur much earlier in people whose memories are intact but whose brain scans show early, preclinical evidence of Alzheimer’s.

    The findings potentially could help doctors identify people at risk of Alzheimer’s earlier than currently is possible. That’s important because Alzheimer’s damage can take root in the brain 15 to 20 years before clinical symptoms appear.

    The research is published Jan. 29 in the journal JAMA Neurology.

    “It wasn’t that the people in the study were sleep-deprived,” said first author Erik S. Musiek, MD, PhD, an assistant professor of neurology. “But their sleep tended to be fragmented. Sleeping for eight hours at night is very different from getting eight hours of sleep in one-hour increments during daytime naps.”

    The researchers also conducted a separate study in mice, to be published Jan. 30 in The Journal of Experimental Medicine, showing that similar circadian disruptions accelerate the development of amyloid plaques in the brain, which are linked to Alzheimer’s.

    Previous studies at Washington University, conducted in people and in animals, have found that levels of amyloid fluctuate in predictable ways during the day and night. Amyloid levels decrease during sleep, and several studies have shown that levels increase when sleep is disrupted or when people don’t get enough deep sleep, according to research by senior author, Yo-El Ju, MD.

    “In this new study, we found that people with preclinical Alzheimer’s disease had more fragmentation in their circadian activity patterns, with more periods of inactivity or sleep during the day and more periods of activity at night,” said Ju, an assistant professor of neurology.

    The researchers tracked circadian rhythms in 189 cognitively normal, older adults with an average age of 66. Some had positron emission tomography (PET) scans to look for Alzheimer’s-related amyloid plaques in their brains. Others had their cerebrospinal fluid tested for Alzheimer’s-related proteins. And some had both scans and spinal fluid testing.

    Of the participants, 139 had no evidence of the amyloid protein that signifies preclinical Alzheimer’s. Most had normal sleep/wake cycles, although several had circadian disruptions that were linked to advanced age, sleep apnea or other causes.

    But among the other 50 subjects — who either had abnormal brain scans or abnormal cerebrospinal fluid — all experienced significant disruptions in their internal body clocks, determined by how much rest they got at night and how active they were during the day. Disruptions in the sleep/wake cycle remained even after the researchers statistically controlled for sleep apnea, age and other factors.

    The study subjects, from Washington University’s Knight Alzheimer’s Disease Research Center, all wore devices similar to exercise trackers for one to two weeks. Each also completed a detailed sleep diary every morning.

    By tracking activity during the day and night, the researchers could tell how scattered rest and activity were throughout 24-hour periods. Subjects who experienced short spurts of activity and rest during the day and night were more likely to have evidence of amyloid buildup in their brains.

    These findings in people reinforce the mouse research from Musiek’s lab. In that study, working with first author Geraldine J. Kress, PhD, an assistant professor of neurology, Musiek studied circadian rhythm disruptions in a mouse model of Alzheimer’s. To disrupt the animals’ circadian rhythms, his team disabled genes that control the circadian clock.

    “Over two months, mice with disrupted circadian rhythms developed considerably more amyloid plaques than mice with normal rhythms,” Musiek said. “The mice also had changes in the normal, daily rhythms of amyloid protein in the brain. It’s the first data demonstrating that the disruption of circadian rhythms could be accelerating the deposition of plaques.”

    Both Musiek and Ju said it’s too early to answer the chicken-and-egg question of whether disrupted circadian rhythms put people at risk for Alzheimer’s disease or whether Alzheimer’s-related changes in the brain disrupt circadian rhythms.

    “At the very least, these disruptions in circadian rhythms may serve as a biomarker for preclinical disease,” said Ju. “We want to bring back these subjects in the future to learn more about whether their sleep and circadian rhythm problems lead to increased Alzheimer’s risk or whether the Alzheimer’s disease brain changes cause sleep/wake cycle and circadian problems.”

    Reference: Kress, GJ, Liao F, Dimitry J, Cedeno MR, Fitzgerald GA, Holtzman DM, Musiek ES. Regulation of amyloid-beta dynamics and pathology by the circadian clock. The Journal of Experimental Medicine, Jan. 30, 2018.


  2. Study looks at personality changes during transition to developing mild cognitive impairment

    February 7, 2018 by Ashley

    From the American Geriatrics Society press release:

    A key feature of Alzheimer’s disease is memory loss and losing one’s ability to think and make decisions (also called “cognitive ability“). Those changes can begin slowly, during a phase called “mild cognitive impairment” (or MCI). A variety of diseases can cause MCI, but the most common is Alzheimer’s disease.

    Not all people who have MCI develop Alzheimer’s disease — but if memory loss is a person’s key MCI symptom, and if that person’s genes (DNA) suggests they may be likely to develop Alzheimer’s disease, the risk for the condition can be as high as 90 percent.

    Personality changes and behavior problems that come with Alzheimer’s disease are as troubling as memory loss and other mental difficulties for caregivers and those living with the condition. Mayo Clinic researchers wondered if personality changes that begin early, when MCI memory loss becomes noticeable, might help predict Alzheimer’s disease at its earliest stages. The researchers created a study to test their theory and published their findings in the Journal of the American Geriatrics Society.

    Researchers recruited cognitively normal participants 21-years-old and older who were genetically more likely to develop Alzheimer’s disease. The recruitment period began in January 1994 and ended in December 2016. Researchers also recruited people without a genetic likelihood for developing Alzheimer’s disease to serve as a control group. All participants took several tests, including medical and neurological (or brain) exams. They were also screened for depression, as well as cognitive and physical function.

    After analyzing results, the researchers concluded that personality changes, which can lead to changes in behavior, occur early on during the development of Alzheimer’s disease. The behavioral changes, however, may be barely noticeable, and can include mood swings, depression, and anxiety. They suggested that further research might be needed to learn whether diagnosing these early personality changes could help experts develop earlier, safer, and more effective treatments — or even prevention options — for the more severe types of behavior challenges that affect people with Alzheimer’s disease.


  3. Anxiety: An early indicator of Alzheimer’s disease?

    January 25, 2018 by Ashley

    From the Brigham and Women’s Hospital press release:

    A new study suggests an association between elevated amyloid beta levels and the worsening of anxiety symptoms. The findings support the hypothesis that neuropsychiatric symptoms could represent the early manifestation of Alzheimer’s disease in older adults.

    Alzheimer’s disease is a neurodegenerative condition that causes the decline of cognitive function and the inability to carry out daily life activities. Past studies have suggested depression and other neuropsychiatric symptoms may be predictors of AD’s progression during its “preclinical” phase, during which time brain deposits of fibrillar amyloid and pathological tau accumulate in a patient’s brain. This phase can occur more than a decade before a patient’s onset of mild cognitive impairment. Investigators at Brigham and Women’s Hospital examined the association of brain amyloid beta and longitudinal measures of depression and depressive symptoms in cognitively normal, older adults. Their findings, published today by The American Journal of Psychiatry, suggest that higher levels of amyloid beta may be associated with increasing symptoms of anxiety in these individuals. These results support the theory that neuropsychiatric symptoms could be an early indicator of AD.

    “Rather than just looking at depression as a total score, we looked at specific symptoms such as anxiety. When compared to other symptoms of depression such as sadness or loss of interest, anxiety symptoms increased over time in those with higher amyloid beta levels in the brain,” said first author Nancy Donovan, MD, a geriatric psychiatrist at Brigham and Women’s Hospital. “This suggests that anxiety symptoms could be a manifestation of Alzheimer’s disease prior to the onset of cognitive impairment. If further research substantiates anxiety as an early indicator, it would be important for not only identifying people early on with the disease, but also, treating it and potentially slowing or preventing the disease process early on.” As anxiety is common in older people, rising anxiety symptoms may prove to be most useful as a risk marker in older adults with other genetic, biological or clinical indicators of high AD risk.

    Researchers derived data from the Harvard Aging Brain Study, an observational study of older adult volunteers aimed at defining neurobiological and clinical changes in early Alzheimer’s disease. The participants included 270 community dwelling, cognitively normal men and women, between 62 and 90 years old, with no active psychiatric disorders. Individuals also underwent baseline imaging scans commonly used in studies of Alzheimer’s disease, and annual assessments with the 30-item Geriatric Depression Scale (GDS), an assessment used to detect depression in older adults.

    The team calculated total GDS scores as well as scores for three clusters symptoms of depression: apathy-anhedonia, dysphoria, and anxiety. These scores were looked at over a span of five years.

    From their research, the team found that higher brain amyloid beta burden was associated with increasing anxiety symptoms over time in cognitively normal older adults. The results suggest that worsening anxious-depressive symptoms may be an early predictor of elevated amyloid beta levels — and, in turn AD — and provide support for the hypothesis that emerging neuropsychiatric symptoms represent an early manifestation of preclinical Alzheimer’s disease.

    Donovan notes further longitudinal follow-up is needed to determine whether these escalating depressive symptoms give rise to clinical depression and dementia stages of Alzheimer’s disease over time.


  4. Blueberry vinegar improves memory in mice with amnesia

    January 9, 2018 by Ashley

    From the American Chemical Society press release:

    Dementia affects millions of people worldwide, robbing them of their ability to think, remember and live as they once did. In the search for new ways to fight cognitive decline, scientists report in ACS’ Journal of Agricultural and Food Chemistry that blueberry vinegar might offer some help. They found that the fermented product could restore cognitive function in mice.

    Recent studies have shown that the brains of people with Alzheimer’s disease, the most common form of dementia, have lower levels of the signaling compound acetylcholine and its receptors. Research has also demonstrated that blocking acetylcholine receptors disrupts learning and memory. Drugs to stop the breakdown of acetylcholine have been developed to fight dementia, but they often don’t last long in the body and can be toxic to the liver. Natural extracts could be a safer treatment option, and some animal studies suggest that these extracts can improve cognition. Additionally, fermentation can boost the bioactivity of some natural products. So Beong-Ou Lim and colleagues wanted to test whether vinegar made from blueberries, which are packed with a wide range of active compounds, might help prevent cognitive decline.

    To carry out their experiment, the researchers administered blueberry vinegar to mice with induced amnesia. Measurements of molecules in their brains showed that the vinegar reduced the breakdown of acetylcholine and boosted levels of brain-derived neurotrophic factor, a protein associated with maintaining and creating healthy neurons. To test how the treatment affected cognition, the researchers analyzed the animals’ performance in mazes and an avoidance test, in which the mice would receive a low-intensity shock in one of two chambers. The treated rodents showed improved performance in both of these tests, suggesting that the fermented product improved short-term memory. Thus, although further testing is needed, the researchers say that blueberry vinegar could potentially be a promising food to help treat amnesia and cognitive decline related to aging.


  5. First brain training exercise positively linked to dementia prevention identified

    December 19, 2017 by Ashley

    From the Indiana University press release:

    Aging research specialists have identified, for the first time, a form of mental exercise that can reduce the risk of dementia.

    The cognitive training, called speed of processing, showed benefits up to 10 years after study participants underwent the mental exercise program, said Frederick W. Unverzagt, PhD, professor of psychiatry at Indiana University School of Medicine.

    The proportion of participants who underwent the training and later developed dementia was significantly smaller than among those who received no cognitive training, the researchers said.

    There were measurable benefits even though the amount of training was small and spread out over time: 10 one-hour sessions over six weeks initially and up to eight booster sessions after that.

    “We would consider this a relatively small dose of training, a low intensity intervention. The persistence — the durability of the effect was impressive,” said Dr. Unverzagt, who explains more in a Q&A blog post.

    Results from the Advanced Cognitive Training in Vital Elderly — ACTIVE — study of 2,802 older adults were recently reported in Alzheimer & Dementia Translational Research and Clinical Interventions, a peer-reviewed journal of the Alzheimer’s Association.

    The researchers, from IU, the University of South Florida, Pennsylvania State University and Moderna Therapeutics, examined healthy adults aged 65 years and older from multiple sites and who were randomly assigned to one of four treatment groups:

    • Participants who received instructions and practice in strategies to improve memory of life events and activities.
    • Participants who received instruction and practice in strategies to help with problem solving and related issues.
    • Participants who received computer-based speed of processing exercises — exercises designed to increase the amount and complexity of information they could process quickly.
    • A control group whose members did not participate in any cognitive training program.

    Initial training consisted of 10 sessions lasting about an hour, over a period of five to six weeks. A subset of participants who completed least 80 percent of the first round of training sessions were eligible to receive booster training, which consisted of four 60 to 75-minute sessions 11 months and 35 months following the initial training. Participants were assessed immediately after training and at one, two, three, five and 10 years after training.

    After attrition due to death and other factors, 1,220 participants completed the 10-year follow-up assessment. During that time, 260 participants developed dementia. The risk of developing dementia was 29 percent lower for participants in speed of processing training than for those who were in the control group, a statistically significant difference. Moreover, the benefits of the training were stronger for those who underwent booster training. While the memory and reasoning training also showed benefits for reducing dementia risk, the results were not statistically significant.

    Dr. Unverzagt noted that the speed of processing training used computerized “adaptive training” software with touch screens. Participants were asked to identify objects in the center of the screen, while also identifying the location of briefly appearing objects in the periphery. The software would adjust the speed and difficulty of the exercises based on how well participants performed.

    In contrast the memory and reasoning programs used more traditional instruction and practice techniques as might occur in a classroom setting.

    Earlier studies had shown that ACTIVE cognitive training improved participants’ cognitive abilities and the ease of engaging in activities of daily living five and 10 years after the initial training. However, an examination of the role of ACTIVE cognitive training on dementia incidence was not significant after five years of follow-up.


  6. Study links canola oil to worsened memory and learning ability in Alzheimer’s

    December 17, 2017 by Ashley

    From the Temple University Health System press release:

    Canola oil is one of the most widely consumed vegetable oils in the world, yet surprisingly little is known about its effects on health. Now, a new study published online December 7 in the journal Scientific Reports by researchers at the Lewis Katz School of Medicine at Temple University (LKSOM) associates the consumption of canola oil in the diet with worsened memory, worsened learning ability and weight gain in mice which model Alzheimer’s disease. The study is the first to suggest that canola oil is more harmful than healthful for the brain.

    “Canola oil is appealing because it is less expensive than other vegetable oils, and it is advertised as being healthy,” explained Domenico Praticò, MD, Professor in the Departments of Pharmacology and Microbiology and Director of the Alzheimer’s Center at LKSOM, as well as senior investigator on the study. “Very few studies, however, have examined that claim, especially in terms of the brain.”

    Curious about how canola oil affects brain function, Dr. Praticò and Elisabetta Lauretti, a graduate student in Dr. Pratico’s laboratory at LKSOM and co-author on the new study, focused their work on memory impairment and the formation of amyloid plaques and neurofibrillary tangles in an Alzheimer’s disease mouse model. Amyloid plaques and phosphorylated tau, which is responsible for the formation of tau neurofibrillary tangles, contribute to neuronal dysfunction and degeneration and memory loss in Alzheimer’s disease. The animal model was designed to recapitulate Alzheimer’s in humans, progressing from an asymptomatic phase in early life to full-blown disease in aged animals.

    Dr. Praticò and Lauretti had previously used the same mouse model in an investigation of olive oil, the results of which were published earlier in 2017. In that study, they found that Alzheimer mice fed a diet enriched with extra-virgin olive oil had reduced levels of amyloid plaques and phosphorylated tau and experienced memory improvement. For their latest work, they wanted to determine whether canola oil is similarly beneficial for the brain.

    The researchers started by dividing the mice into two groups at six months of age, before the animals developed signs of Alzheimer’s disease. One group was fed a normal diet, while the other was fed a diet supplemented with the equivalent of about two tablespoons of canola oil daily.

    The researchers then assessed the animals at 12 months. One of the first differences observed was in body weight — animals on the canola oil-enriched diet weighed significantly more than mice on the regular diet. Maze tests to assess working memory, short-term memory, and learning ability uncovered additional differences. Most significantly, mice that had consumed canola oil over a period of six months suffered impairments in working memory.

    Examination of brain tissue from the two groups of mice revealed that canola oil-treated animals had greatly reduced levels of amyloid beta 1-40. Amyloid beta 1-40 is the more soluble form of the amyloid beta proteins. It generally is considered to serve a beneficial role in the brain and acts as a buffer for the more harmful insoluble form, amyloid beta 1-42.

    As a result of decreased amyloid beta 1-40, animals on the canola oil diet further showed increased formation of amyloid plaques in the brain, with neurons engulfed in amyloid beta 1-42. The damage was accompanied by a significant decrease in the number of contacts between neurons, indicative of extensive synapse injury. Synapses, the areas where neurons come into contact with one another, play a central role in memory formation and retrieval.


  7. PET tracer gauges effectiveness of promising Alzheimer’s treatment

    by Ashley

    From the Society of Nuclear Medicine and Molecular Imaging press release:

    In the December featured basic science article in The Journal of Nuclear Medicine, Belgian researchers report on the first large-scale longitudinal imaging study to evaluate BACE1 inhibition with micro-PET in mouse models of Alzheimer’s disease. PET imaging has been established as an excellent identifier of the amyloid plaque and tau tangles that characterize Alzheimer’s disease. Now it is proving to be an effective way to gauge treatment effectiveness.

    The tracer makes it possible to image the effects of chronic administration of an inhibitor for an enzyme, called beta (?)-site amyloid precursor protein-cleaving enzyme 1 (BACE1), which cuts off protein fragments that can lead to amyloid-? development and is more prevalent in brains affected by Alzheimer’s. It does this by binding to BACE1.

    The study compared control mice with those genetically-altered to have Alzheimer’s, and tested 18F-florbetapir (18F-AV45) along with two other tracers, 18F-FDG PET and 18F-PBR111. The mice received the BACE inhibitor at 7 weeks, then brain metabolism, neuroinflammation and amyloid-? pathology were measured using a micro-PET (?PET) scanner and each of the tracers. Baseline scans were done at 6-7 weeks and follow-up scans at 4,7 and 12 months. 18F-AV45 uptake was measured at 8 and 13 months of age. After the final scans, microscopic studies were performed.

    While all three tracers detected pathological differences between the genetically modified mice and the controls, only 18F-AV45 showed the effects of inhibitor treatment by identifying reduced amyloid-? pathology in the genetically modified mice. This was confirmed in the microscopic studies.

    The team of the Molecular Imaging Center Antwerp, Belgium, however warns, “This study clearly showed that accurate quantification of amyloid-beta tracers is critically important and that the non-specific uptake in the brain of subjects might be underestimated for some existing Alzheimer’s tracers that have fast metabolization profiles. The aim of this translational research is advancing results discovered at the bench so that they can be applied to patients at the bedside.”

    The statistics on Alzheimer’s are sobering. Approximately 10 percent of people 65 and older have Alzheimer’s dementia, according to the Alzheimer’s Association. More than 5 million Americans are living with the disease, and that number could rise to 16 million by 2050.


  8. Study suggests some video games are good for older adults’ brains

    December 15, 2017 by Ashley

    From the Université de Montréal press release:

    If you’re between 55 and 75 years old, you may want to try playing 3D platform games like Super Mario 64 to stave off mild cognitive impairment and perhaps even prevent Alzheimer’s disease.

    That’s the finding of a new Canadian study by Université de Montréal psychology professors Gregory West, Sylvie Belleville and Isabelle Peretz. Published in PLOS ONE, it was done in cooperation with the Institut universitaire de gériatrie de Montréal (IUGM), Benjamin Rich Zendel of Memorial University in Newfoundland, and Véronique Bohbot of Montreal’s Douglas Hospital Research Centre.

    In two separate studies, in 2014 and 2017, young adults in their twenties were asked to play 3D video games of logic and puzzles on platforms like Super Mario 64. Findings showed that the gray matter in their hippocampus increased after training.

    The hippocampus is the region of the brain primarily associated with spatial and episodic memory, a key factor in long-term cognitive health. The gray matter it contains acts as a marker for neurological disorders that can occur over time, including mild cognitive impairment and Alzheimer’s.

    West and his colleagues wanted to see if the results could be replicated among healthy seniors.

    The research team recruited 33 people, ages 55 to 75, who were randomly assigned to three separate groups. Participants were instructed to play Super Mario 64 for 30 minutes a day, five days a week, take piano lessons (for the first time in their life) with the same frequency and in the same sequence, or not perform any particular task.

    The experiment lasted six months and was conducted in the participants’ homes, where the consoles and pianos, provided by West’s team, were installed.

    The researchers evaluated the effects of the experiment at the beginning and at the end of the exercise, six months later, using two different measurements: cognitive performance tests and magnetic resonance imaging (MRI) to measure variations in the volume of gray matter. This enabled them to observe brain activity and any changes in three areas:

    • the dorsolateral prefrontal cortex that controls planning, decision-making and inhibition;
    • the cerebellum that plays a major role in motor control and balance; and
    • the hippocampus, the centre of spatial and episodic memory.

    According to the MRI test results, only the participants in the video-game cohort saw increases in gray matter volume in the hippocampus and cerebellum. Their short-term memory also improved.

    The tests also revealed gray matter increases in the dorsolateral prefrontal cortex and cerebellum of the participants who took piano lessons, whereas some degree of atrophy was noted in all three areas of the brain among those in the passive control group.

    What mechanism triggers increases in gray matter, especially in the hippocampus, after playing video games? “3-D video games engage the hippocampus into creating a cognitive map, or a mental representation, of the virtual environment that the brain is exploring.,” said West. “Several studies suggest stimulation of the hippocampus increases both functional activity and gray matter within this region.”

    Conversely, when the brain is not learning new things, gray matter atrophies as people age. “The good news is that we can reverse those effects and increase volume by learning something new, and games like Super Mario 64, which activate the hippocampus, seem to hold some potential in that respect,” said West. Added Belleville: “These findings can also be used to drive future research on Alzheimer’s, since there is a link between the volume of the hippocampus and the risk of developing the disease.”

    “It remains to be seen,” concluded West, “whether it is specifically brain activity associated with spatial memory that affects plasticity, or whether it’s simply a matter of learning something new.”


  9. Study suggests genes behind higher education linked to lower risk of Alzheimer’s

    by Ashley

    From the Karolinska Institutet press release:

    Using genetic information, researchers at Karolinska Institutet in Sweden provide new evidence that higher educational attainment is strongly associated with a lower risk of Alzheimer’s disease.

    The causes of Alzheimer’s disease are largely unknown and treatment trials have been disappointing. This has led to increasing interest in the potential for reducing the disease by targeting modifiable risk factors. Many studies have found that education and vascular risk factors are associated with the risk of Alzheimer’s disease, but whether these factors actually cause Alzheimer’s has been difficult to disentangle.

    Mendelian randomisation is a method that uses genetic information to make causal inferences between potential risk factors and disease. If a gene with a specific impact on the risk factor is also associated with the disease, then this indicates that the risk factor is a cause of the disease.

    Susanna C. Larsson, associate professor at the Institute of Environmental Medicine at Karolinska Institutet, and colleagues in Cambridge and Munich, used the Mendelian randomisation approach to assess whether education and different lifestyle and vascular risk factors are associated with Alzheimer’s disease. The analysis included more than 900 genetic variants previously shown to be associated with the risk factors. Comparisons of these genetic variants among 17,000 patients with Alzheimer’s disease and 37,000 healthy controls revealed a strong association for genetic variants that predict education.

    “Our results provide the strongest evidence so far that higher educational attainment is associated with a lower risk of Alzheimer’s disease. Therefore, improving education may substantially decrease the number of people developing this devastating disease,” says Susanna C. Larsson.

    According to the researchers, one possible explanation for this link is ‘cognitive reserve‘, which refers to the ability to recruit and use alternative brain networks or structures not normally used in order to compensate for brain ageing.

    “Evidence suggests that education helps improve brain networks and thus could increase this reserve,” says Susanna C. Larsson.

    The study was financed by the European Union’s Horizon 2020 research and innovation programme and the Swedish Brain Foundation.


  10. Study identifies gene variant that protects against Alzheimer’s disease

    December 11, 2017 by Ashley

    From the Brigham Young University press release:

    Research published Wednesday in Genome Medicine details a novel and promising approach in the effort to treat Alzheimer’s disease.

    Brigham Young University professors Perry Ridge and John Kauwe led the discovery of a rare genetic variant that provides a protective effect for high-risk individuals — elderly people who carry known genetic risk factors for Alzheimer’s — who never acquired the disease.

    In other words, there’s a specific reason why people who should get Alzheimer’s remain healthy. Study authors believe this genetic function could be targeted with drugs to help reduce the risk of people getting the disease.

    “Instead of identifying genetic variants that are causing disease, we wanted to identify genetic variants that are protecting people from developing disease,” said Ridge, assistant professor of biology at BYU. “And we were able to identify a promising genetic variant.”

    That former approach to Alzheimer’s disease has been generally effective in producing a list of genes that might impact risk for the disease, but it leaves researchers without sufficient data on what to do next. In this new approach, Ridge and Kauwe develop the biological mechanism by which a genetic variant actually impacts Alzheimer’s disease.

    Using data from the Utah Population Database — a 20-million-record database of the LDS Church’s genealogical records combined with historical medical records from Utah — Ridge and Kauwe first identified families that had a large number of resilient individuals: those who carried the main genetic risk factor for Alzheimer’s (E4 Allele) but remained healthy into advanced age.

    Using whole genome sequencing and a linkage analysis methodology, they then looked for the DNA that those resilient individuals shared with each other that they didn’t share with loved ones who died of Alzheimer’s. They discovered the resilient subjects shared a variant in the RAB10 gene while those who got the disease did not share the genetic variant.

    Once the researchers identified the potentially protective gene variant, they over expressed it in cells and under expressed it in cells to see the impact on Alzheimer’s disease related proteins. They learned that when this gene is reduced in your body, it has the potential to reduce your risk for Alzheimer’s.

    “There are currently no meaningful interventions for Alzheimer disease; No prevention, no modifying therapies, no cure,” Kauwe said. “The discoveries we’re reporting in this manuscript provide a new target with a new mechanism that we believe has great potential to impact Alzheimer’s disease in the future.”