The Brain: Alzheimer's and dementia news and discussions

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weatheriscool
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Study links target protein for diabetes drug to reduced risk of Alzheimer's disease
https://medicalxpress.com/news/2022-06- ... eimer.html
by Karolinska Institutet

Mechanisms associated with a particular diabetes drug can also help to protect against Alzheimer's disease, a study by researchers at Karolinska Institutet in Sweden and published in Neurology reports. The results indicate that the drug's target protein could be an interesting candidate for the treatment of Alzheimer's disease.

Alzheimer's disease is becoming increasingly common, but there are no drugs to affect the course of the disease and the development of new drugs is a slow, costly and complex process.

An alternative strategy is therefore to find already approved drugs that can prove efficacious against the disease and give them a new area of application. Diabetes drugs have been put forward as possible candidates, but so far the studies that have tested diabetes drugs for Alzheimer's disease have not produced convincing results.

In the present study, researchers from Karolinska Institutet used genetic methods to study this more closely.

"Genetic variants within or nearby the genes that encode a drug's target proteins can cause physiological changes similar to the effects of the drug," says the study's first author Bowen Tang, doctoral student at the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet. "We utilize such variants to test the repurposing potential of already approved drugs."
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Three distinct brain circuits in the thalamus contribute to Parkinson's symptoms
https://medicalxpress.com/news/2022-06- ... ibute.html
by Sarah McDonnell, Massachusetts Institute of Technology

Parkinson's disease is best-known as a disorder of movement. Patients often experience tremors, loss of balance, and difficulty initiating movement. The disease also has lesser-known symptoms that are nonmotor, including depression.

In a study of a small region of the thalamus, MIT neuroscientists have now identified three distinct circuits that influence the development of both motor and nonmotor symptoms of Parkinson's. Furthermore, they found that by manipulating these circuits, they could reverse Parkinson's symptoms in mice.

The findings suggest that those circuits could be good targets for new drugs that could help combat many of the symptoms of Parkinson's disease, the researchers say.

"We know that the thalamus is important in Parkinson's disease, but a key question is how can you put together a circuit that that can explain many different things happening in Parkinson's disease. Understanding different symptoms at a circuit level can help guide us in the development of better therapeutics," says Guoping Feng, the James W. and Patricia T. Poitras Professor in Brain and Cognitive Sciences at MIT, a member of the Broad Institute of Harvard and MIT, and the associate director of the McGovern Institute for Brain Research at MIT.

Feng is the senior author of the study, which appears today in Nature. Ying Zhang, a J. Douglas Tan Postdoctoral Fellow at the McGovern Institute, and Dheeraj Roy, a NIH K99 Awardee and a McGovern Fellow at the Broad Institute, are the lead authors of the paper.
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Research finds that social isolation is directly associated with later dementia
https://medicalxpress.com/news/2022-06- ... entia.html
by American Academy of Neurology


Social isolation is linked to lower brain volume in areas related to cognition and a higher risk of dementia, according to research published in the June 8, 2022, online issue of Neurology. The study found that social isolation was linked to a 26% increased risk of dementia, separately from risk factors like depression and loneliness.

"Social isolation is a serious yet underrecognized public health problem that is often associated with old age," said study author Jianfeng Feng, Ph.D., of Fudan University in Shanghai, China. "In the context of the COVID-19 pandemic, social isolation, or the state of being cut off from social networks, has intensified. It's more important than ever to identify people who are socially isolated and provide resources to help them make connections in their community."

The study looked at 462,619 people across the United Kingdom with an average age of 57 at the beginning of the study who were followed for nearly 12 years before the pandemic. Of those, 41,886, or 9% of people reported being socially isolated, and 29,036, or 6% of people felt lonely. During the study, 4,998 developed dementia.
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Multiple heart-related conditions linked to triple dementia risk, regardless of genetics

by University of Exeter
https://medicalxpress.com/news/2022-06- ... riple.html
Having multiple conditions that affect the heart is linked to a greater risk of dementia than having high genetic risk, according to a new large-scale study.

Led by Oxford University and the University of Exeter, the study is among the largest ever to examine the link between several heart-related conditions and dementia, and one of the few to look at the complex issue of multiple health conditions.

Published in The Lancet Healthy Longevity, the paper looked at data from more than 200,000 people, aged 60 or above and of European ancestry, in UK Biobank. The international research team identified those who had been diagnosed with the cardiometabolic conditions diabetes, stroke, or a heart attack, or any combination of the three, and those who went on to develop dementia.

Within this study population, the researchers found that the more of these three conditions a person had, the higher their risk of dementia. People who had all three conditions were three times more likely to develop dementia than people who had a high genetic risk.

Dr. Xin You Tai, lead author and doctoral student at University of Oxford, said, "Dementia is a major global issue, with predictions that 135 million worldwide will have the devastating condition by 2050. We found that having such heart-related conditions is linked to dementia risk to a greater extent than genetic risk. So whatever genetic risk you were born with, you can potentially make a big impact on reducing risk of dementia by looking after heart and metabolic health throughout life."
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Clinical trial suggests Parkinson's drug is safe in humans
https://medicalxpress.com/news/2022-06- ... -safe.html
by Bob Yirka , Medical Xpress

A large team of researchers from Denali Therapeutics, working with colleagues from multiple entities in the U.S. and one in Canada, has found that a LRRK2 inhibitor called DNL201 showed no ill effects to volunteers in a clinical trial. In their paper published in Science Translational Medicine, the group describes their clinical trial of the Parkinson's drug and what they learned during its run. Patrick Lewis, with Royal Veterinary College London has published a Focus piece in the same journal issue outlining the work being done by the team at Denali.

Parkinson's disease is a disease that results from the destruction of neurons in the brain that produce dopamine, which is critical for motor function. Prior research has suggested it comes about most often due to environmental factors in people with a genetic risk for it. Prior research has also shown that mutated versions of a certain gene lead to overproduction of an enzyme called LRRK2, which leads to inflammation and other problems. Currently, there are no therapies available to slow its progression.

One of the hallmarks of Parkinson's is elevated levels of the LRRK2 enzyme which damage lysosomes—organelles responsible for removing toxins from cells in the brain. This leads to a buildup of toxins and cell death. Prior work involved in developing drugs to stop the progression of Parkinson's has centered around reducing such levels. In this new effort, the researchers have developed a drug called DNL201 that has shown promise. It has been tested in animals, where it has effectively reduced LRRK2 enzyme levels. But in some animals, it has also led to a dangerous side effect, where sacks inside cells in the lungs and kidneys swell. In this new clinical trial, the goal was to determine if DNL201 was safe for use in humans, not to assess whether it slowed the progression of Parkinson's.
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Uncovering links between grit and cognitive function
https://medicalxpress.com/news/2022-06- ... ction.html
by Public Library of Science
A new analysis of the personality trait of grit found that people who showed higher levels of grit also had different patterns of cognitive performance—but not necessarily enhanced cognitive performance. Nuria Aguerre of the University of Granada, Spain, and colleagues present these findings in the open-access journal PLOS ONE on June 22, 2022.

A person with grit is someone who displays notable perseverance in pursuit of long-term goals, even in the face of setbacks. Researchers typically measure it with an evaluation tool known as the Grit Scale. While previous studies have suggested a potential link between grit and certain aspects of cognitive functioning, no studies have directly examined this relationship.

To gain further insight, Aguerre and colleagues had 134 study participants complete questionnaires, including the Grit Scale, to evaluate their personalities according to three traits: grit, impulsiveness, and mindfulness. The participants also completed four experimental computer-based tasks to measure different facets of cognitive ability, including flexibility, inhibition, the ability to replace irrelevant items in one's working memory—which holds information temporarily—with newer, relevant items, and the control mode tendency.
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Untangling the role of tau in Alzheimer's disease

https://medicalxpress.com/news/2022-06- ... sease.html
Alzheimer's disease is a brain disorder that causes neurons to die, slowly destroying memory and thinking skills. It's the most common type of dementia, impacting an estimated 50 million people worldwide, and is a particularly serious issue for Japan's super-aged society. Despite its prevalence, the causes remain poorly understood and treatment options are limited.

Now, a team of scientists in Japan has revealed how excess tau—a key protein implicated in Alzheimer's disease—impairs signaling between neurons in the brains of mice. The study, published recently in eLife, could open new pathways for treating the symptoms and even halting the progression of Alzheimer's disease and other neurodegenerative disorders.

Tau is produced in neurons, where it binds to and promotes the assembly of microtubules—long, thin filaments that maintain cell structure and provide pathways for transport within the cell. Tau usually exists in either this bound state, or it is dissolved in the liquid that fills the cell.

However, in some neurological disorders, most famously in Alzheimer's disease, levels of soluble tau in certain brain regions become too high, and it aggregates into insoluble structures called neurofibrillary tangles.
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Study: Flu vaccination linked to 40% reduced risk of Alzheimer's disease

by University of Texas Health Science Center at Houston
https://medicalxpress.com/news/2022-06- ... sease.html
People who received at least one influenza vaccine were 40% less likely than their non-vaccinated peers to develop Alzheimer's disease over the course of four years, according to a new study from UTHealth Houston.

Research led by first author Avram S. Bukhbinder, MD, a recent alumnus of McGovern Medical School at UTHealth Houston, and senior author Paul. E. Schulz, MD, the Rick McCord Professor in Neurology at McGovern Medical School, compared the risk of Alzheimer's disease incidence between patients with and without prior flu vaccination in a large nationwide sample of U.S. adults aged 65 and older.

An early online version of the paper detailing the findings is available in advance of its publication in the Aug. 2 issue of the Journal of Alzheimer's Disease.

"We found that flu vaccination in older adults reduces the risk of developing Alzheimer's disease for several years. The strength of this protective effect increased with the number of years that a person received an annual flu vaccine—in other words, the rate of developing Alzheimer's was lowest among those who consistently received the flu vaccine every year," said Bukhbinder, who is still part of Schulz's research team while in his first year of residency with the Division of Child Neurology at Massachusetts General Hospital. "Future research should assess whether flu vaccination is also associated with the rate of symptom progression in patients who already have Alzheimer's dementia."
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Protecting the brain from dementia-inducing abnormal protein aggregates

by The National Institutes for Quantum Science and Technology
https://medicalxpress.com/news/2022-07- ... gates.html
In order to maintain cellular homeostasis (i.e., a state of equilibrium), cells undergo selective autophagy or self-degradation of unwanted proteins. Autophagy receptors control this process, by mediating the selection of a target protein that is then "cleared."

Tau proteins—which otherwise play an important role in stabilizing and maintaining the internal organization of neurons in the brain—abnormally accumulate inside neurons in conditions like dementia and Alzheimer's disease. This build-up of hyper-phosphorylated tau proteins (or tau oligomers) causes the formation of neurofibrillary tangles (NFTs) and eventual cell death of neurons in the brains of people with dementia, contributing to the disease's progressive neurodegenerative symptoms. Now, while tau proteins can be degraded by selective autophagy, the exact mechanism of how this occurs remains a mystery.
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Uncovering one of the driving forces of Alzheimer's disease
https://medicalxpress.com/news/2022-07- ... sease.html
by Flinders University
Alzheimer's disease, the most common form of dementia, currently has no cure or effective therapy, in part due to gaps in our understanding of how the progressive neurodegenerative disorder arises in the brain.

Now, a Flinders University study has shown how a protein called tau, a critical factor in the development of Alzheimer's disease, turns from normal to a disease state—and demonstrates how this discovery could deliver a therapeutic target.

Published in the journal Science Advances, the team's findings provide hope for preventing the tau transformation process from happening, thereby keeping tau in a healthy state and avoiding toxic effects on brain cells.

"Alongside a small peptide called amyloid-beta, the tau protein is a central factor in Alzheimer's disease. Tau is necessary for the toxic effects on brain cells that then result in impaired memory function," says senior study author Dr. Arne Ittner, Senior Research Fellow in Neuroscience in the Flinders Health and Medical Research Institute.
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