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."
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.
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.
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."
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.
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.
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.
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."
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.
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.
A joint research team from the LKS Faculty of Medicine, The University of Hong Kong (HKUMed) and City University of Hong Kong (CityU) has discovered that the electrical stimulation of the eye surface can alleviate depression-like symptoms and improve cognitive function in animal models. These significant findings were recently published in Brain Stimulation and the Annals of the New York Academy of Sciences.
Major depression is the most common and severe psychiatric disorder across the world. Recently, the World Health Organization reported that the COVID-19 pandemic had triggered a massive increase in the number of people with anxiety and depression. About a quarter of patients do not respond adequately to the treatments available.
Dr. Lim Lee Wei, Assistant Professor in the School of Biomedical Sciences, HKUMed, and a former Lee Kuan Yew Research Fellow in Singapore, reported in 2015 that deep brain stimulation of the prefrontal cortex in the brains of animals could improve memory function and relieve depressive symptoms. These therapeutic effects were attributed to the growth of brain cells in the hippocampus, a region of the brain known to be involved in learning and memory function. However, this technique, also known as deep brain stimulation, is invasive and requires surgery to implant electrodes in the brain, which may cause side effects such as infections and other post-operative complications.
by University of Texas Health Science Center at Houston
A novel, disease-modifying therapy for Alzheimer's disease may involve the whole exchange of blood, which effectively decreased the formation of amyloid plaque in the brains of mice, according to a new study from UTHealth Houston.
A research team led by senior author Claudio Soto, Ph.D., professor in the Department of Neurology with McGovern Medical School at UTHealth Houston, in collaboration with first author Akihiko Urayama, Ph.D., associate professor in the department, performed a series of whole blood exchange treatments to partially replace blood from mice exhibiting Alzheimer's disease-causing amyloid precursor proteins with complete blood from healthy mice of the same genetic background. The results of the study were published today in Molecular Psychiatry.
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A new computer algorithm developed by the University of Toronto's Parham Aarabi can store and recall information strategically—just like our brains.
The associate professor in the Edward S. Rogers Sr. department of electrical and computer engineering, in the Faculty of Applied Science & Engineering, has also created an experimental tool that leverages the new algorithm to help people with memory loss.
"Most people think of AI as more robot than human," says Aarabi, whose framework is explored in a paper being presented this week at the IEEE Engineering in Medicine and Biology Society Conference in Glasgow. "I think that needs to change."
In the past, computers have relied on their users to tell them exactly what information to store. But with the rise of artificial intelligence (AI) techniques such as deep learning and neural nets, there has been a move toward "fuzzier" approaches.
"Ten years ago, computing was all about absolutes," says Aarabi. "CPUs processed and stored memory data in an exact way to make binary decisions. There was no ambiguity.
"Now we want our computers to make approximate conclusions and guess percentages. We want an image processor to tell us, for example, that there's a 10 percent chance a picture contains a car and a 40 percent chance that it contains a pedestrian."
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Consumption of seven or more units of alcohol per week is associated with higher iron levels in the brain, according to a study of almost 21,000 people publishing July 14 in the open access journal PLOS Medicine. Iron accumulation in the brain has been linked with Alzheimer's and Parkinson's diseases and is a potential mechanism for alcohol-related cognitive decline.
There is growing evidence that even moderate alcohol consumption can adversely impact brain health. Anya Topiwala of the University of Oxford, United Kingdom, and colleagues explored relationships between alcohol consumption and brain iron levels. Their 20,965 participants from the UK Biobank reported their own alcohol consumption, and their brains were scanned using magnetic resonance imaging (MRI). Almost 7,000 also had their livers imaged using MRI to assess levels of systemic iron. All individuals completed a series of simple tests to assess cognitive and motor function.
Parkinson's is a progressive and debilitating disease of the brain that eventually compromises patients' ability to walk and even to talk. Its diagnosis is complex, and in the early stages—impossible.
The usual method of visualizing brain structure utilizes a technique most of us are familiar with, called MRI. However, it is not sensitive enough to reveal the biological changes that take place in the brain of Parkinson patients, and at present is primarily only used to eliminate other possible diagnoses.
The Hebrew University of Jerusalem (HU) researchers, led by Professor Aviv Mezer, realized that the cellular changes in Parkinson's could possibly be revealed by adapting a related technique, known as quantitative MRI (qMRI). Their method has enabled them to look at microstructures within the part of the deep brain known as the striatum—an organ which is known to deteriorate during the progress of Parkinson's disease. Using a novel method of analysis, developed by Mezer's doctoral student, Elior Drori, biological changes in the cellar tissue of the striatum were clearly revealed. Moreover, they were able to demonstrate that these changes were associated with the early stages of Parkinson's and patients' movement dysfunction. Their findings were published today in the journal Science Advances.
Alzheimer's disease can begin almost imperceptibly, often masquerading in the early months or years as forgetfulness that is common in older age. What causes the disease remains largely a mystery.
But researchers at Tufts University and the University of Oxford, using a three-dimensional human tissue culture model mimicking the brain, have shown that varicella zoster virus (VZV), which commonly causes chickenpox and shingles, may activate herpes simplex (HSV), another common virus, to set in motion the early stages of Alzheimer's disease.
Normally HSV-1—one of the main variants of the virus—lies dormant within the neurons of the brain, but when it is activated it leads to accumulation of tau and amyloid beta proteins, and loss of neuronal function—signature features found in patients with Alzheimer's.
One of the hallmarks of Alzheimer's disease is a reduction in the firing of some neurons in the brain, which contributes to the cognitive decline that patients experience. A new study from MIT shows how a type of cells called microglia contribute to this slowdown of neuron activity.
The study found that microglia that express the APOE4 gene, one of the strongest genetic risk factors for Alzheimer's disease, cannot metabolize lipids normally. This leads to a buildup of excess lipids that interferes with nearby neurons' ability to communicate with each other.
"APOE4 is a major genetic risk factor, and many people carry it, so the hope is that by studying APOE4, that will also provide a bigger picture of the fundamental pathophysiology of Alzheimer's disease and what fundamental cell processes have to go wrong to result in Alzheimer's disease," says Li-Huei Tsai, director of MIT's Picower Institute for Learning and Memory and the senior author of the study.
The findings suggest that if researchers could find a way to restore normal lipid metabolism in microglia, that might help to treat some of the symptoms of the disease.
MIT postdoc Matheus Victor is the lead author of the paper, which appears today in Cell Stem Cell.
Huntington's chorea is a hereditary disease that leads to cognitive and motor impairments and death. Scientists at the University of Bremen have worked with international partners to elucidate the mechanism by which the mutated huntingtin protein can be kept at bay.
"We have uncovered a mechanism by which the body's own protein folding helpers keep the mutated huntingtin protein at bay," explains project leader and professor Janine Kirstein at the University of Bremen. Protein-folding helpers allow proteins to take on and maintain their correct structure to perform their multifaceted functions. The researchers were already familiar with three of the helpers, but what they didn't know yet was what the binding with the mutated huntingtin protein looked like, which of the three folding aids could recognize the mutated protein, and what its binding looked like.
"We have now been able to identify this using the crosslinking mass spectrometry method," says the biochemist. This method can precisely determine protein interactions. However, there was still a long way to go in terms of understanding the bond. "It was only through modeling that we were able to better understand the interaction between protein-folding helpers and mutant huntingtin."
A large team of researchers working at the University of Pennsylvania, has found evidence that suggests increased concentrations of the transmembrane protein Glycoprotein Nonmetastatic Melanoma Protein B (GPNMB) in blood samples could be an early biomarker for Parkinson's disease. In their paper published in the journal Science, the group describes how they studied possible risk factors associated with chromosome 7 in Parkinson's disease patients and what they found regarding a link to the GPNMB. Brit Mollenhauer and Christine A. F. von Arnim have published a Perspectives piece in the same journal issue outlining the work done by the team in Philadelphia.
Parkinson's disease is a neurogenerative disease that leads to shaking and stiffness of limbs and appendages along with problems with balance—as the disease progresses, most patients develop problems with walking. Its cause is still under investigation though most in the field believe it is an instance of a genetic disorder making people more susceptible to some still unknown environmental element. And while there are a number of therapies used to treat symptoms (such as dopamine), there is no cure.
Prior research has shown that damage to nerves begins long before patients experience symptoms. For that reason, scientists have been looking for early markers that could be used to allow for earlier diagnosis and treatment. In this new effort, the researchers began their work by noting that, despite the identification of multiple genes that are thought to contribute to a risk for developing the disease, the actual genes involved are still not known. For that reason, they chose to focus their work on the development of a-synuclein (aSyn)—fibrils that form in Parkinson's patients that are a hallmark of the disease.
Researchers at the University of Illinois Chicago have discovered that increasing the production of new neurons in mice with Alzheimer's disease (AD) rescues the animals' memory defects. The study, to be published August 19 in the Journal of Experimental Medicine, shows that new neurons can incorporate into the neural circuits that store memories and restore their normal function, suggesting that boosting neuron production could be a viable strategy to treat AD patients.
New neurons are produced from neural stem cells via a process known as neurogenesis. Previous studies have shown that neurogenesis is impaired in both AD patients and laboratory mice carrying genetic mutations linked to AD, particularly in a region of the brain called the hippocampus that is crucial for memory acquisition and retrieval.
"However, the role of newly formed neurons in memory formation, and whether defects in neurogenesis contribute to the cognitive impairments associated with AD, is unclear," says Professor Orly Lazarov of the Department of Anatomy and Cell Biology in the University of Illinois Chicago College of Medicine.
