The Brain: Alzheimer's and dementia news and discussions

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Brain discovery holds key to boosting body's ability to fight Alzheimer's, multiple sclerosis
https://medicalxpress.com/news/2022-10- ... -body.html
by University of Virginia

UVA Health researchers have discovered a molecule in the brain responsible for orchestrating the immune system's responses to Alzheimer's disease and multiple sclerosis (MS), potentially allowing doctors to supercharge the body's ability to fight those and other devastating neurological diseases.

The molecule the researchers identified, called a kinase, is crucial to both removing plaque buildup associated with Alzheimer's and preventing the debris buildup that causes MS, the researchers found. It does this, the researchers showed, by directing the activity of brain cleaners called microglia. These immune cells were once largely ignored by scientists but have, in recent years, proved vital players in brain health.
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A telltale protein spreads throughout the brain in distinct patterns based on patients' Alzheimer's phenotype
https://medicalxpress.com/news/2022-10- ... terns.html
by Delthia Ricks , Medical Xpress

New imaging of patients with Alzheimer's demonstrates how a telltale protein spreads throughout the brain based on the phenotype of the disease, i.e., whether the condition is dominated by forgetfulness, or atrophy in a specific brain region. The research offers a host of illuminating clues that ultimately may inform new treatment strategies.

The protein is known as tau and a large multi-disciplinary team of brain researchers at McGill University in Montreal has been able to trace the protein's patterns in living patients via magnetic resonance imaging (MRI). Alzheimer's disease is intimately linked to tau, which can form tangles in the brain that irrevocably damage neurons.

The patterns detected by McGill scientists apparently are unique to the phenotype of Alzheimer's afflicting the patient. This staggering finding opens an intriguing new window into the molecular mechanisms of the disease. And while many features of Alzheimer's are the same from one patient to the next, phenotypes are a hallmark of the condition. Tracking tau patterns is a specialty of the scientists at McGill, who found that the intrinsic connectivity of the human brain itself provides the scaffolding for the aggregation of tau in distinct variants of the disease.
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New research suggests nose picking could increase risk for Alzheimer's and dementia
https://medicalxpress.com/news/2022-10- ... entia.html
by Griffith University
Griffith University researchers have demonstrated that a bacteria can travel through the olfactory nerve in the nose and into the brain in mice, where it creates markers that are a tell-tale sign of Alzheimer's disease.

The study, published in the journal Scientific Reports, showed that Chlamydia pneumoniae used the nerve extending between the nasal cavity and the brain as an invasion path to invade the central nervous system. The cells in the brain then responded by depositing amyloid beta protein which is a hallmark of Alzheimer's disease.

Professor James St John, Head of the Clem Jones Center for Neurobiology and Stem Cell Research, is a co-author of the world first research.

"We're the first to show that Chlamydia pneumoniae can go directly up the nose and into the brain where it can set off pathologies that look like Alzheimer's disease," Professor St John said. "We saw this happen in a mouse model, and the evidence is potentially scary for humans as well."

The olfactory nerve in the nose is directly exposed to air and offers a short pathway to the brain, one which bypasses the blood-brain barrier. It's a route that viruses and bacteria have sniffed out as an easy one into the brain.
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Alzheimer's risk gene undermines insulation of brain's 'wiring'
https://medicalxpress.com/news/2022-11- ... brain.html
by Massachusetts Institute of Technology
It's well known that carrying one copy of the APOE4 gene variant increases one's risk for Alzheimer's disease threefold and two copies about tenfold, but the fundamental reasons why and what can be done to help patients remain largely unknown. A study published by an MIT-based team Nov. 16 in Nature provides some new answers as part of a broader line of research that has demonstrated APOE4's consequences cell type by cell type in the brain.

The new study combines evidence from postmortem human brains, lab-based human brain cell cultures, and Alzheimer's model mice to show that when people have one or two copies of APOE4, rather than the more common and risk-neutral APOE3 version, cells called oligodendrocytes mismanage cholesterol, failing to transport the fat molecule to wrap the long vine-like axon "wiring" that neurons project to make brain circuit connections. Deficiency of this fatty insulation, called myelin, may be a significant contributor to the pathology and symptoms of Alzheimer's disease because without proper myelination, communications among neurons are degraded.

Recent studies by the research group, led by Picower Professor Li-Huei Tsai, director of The Picower Institute for Learning and Memory and the Aging Brain Initiative at MIT, have found distinct ways that APOE4 disrupts how fat molecules, or lipids, are handled by key brain cell types including neurons, astrocytes and microglia. In the new study as well as in those, the team has identified compounds that appear in the lab to correct these different problems, yielding potential pharmaceutical-based treatment strategies.

The new study extends that work not only by discovering how APOE4 disrupts myelination, but also by providing the first systematic analysis across major brain cell types using single nucleus RNA sequencing (snRNAseq) to compare how gene expression differs in people with APOE4 compared to APOE3.
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Protein shapes could indicate Parkinson's disease
https://medicalxpress.com/news/2022-11- ... sease.html
by Peter Rüegg, ETH Zurich

ETH Zurich researchers have found that a set of proteins have different shapes in the spinal fluid of healthy individuals and Parkinson's patients. These could be used in the future as a new type of biomarker for this disease.

Many human diseases can be detected and diagnosed using biomarkers in blood or other body fluids. Parkinson's disease is different: to date, there is no such biomarker being used in the clinicto indicate this neurodegenerative disease.

A team led by ETH Zurich Professor Paola Picotti could now help to close this gap. In a study just published in the journal Nature Structural and Molecular Biology, the researchers present 76 proteins that might serve as biomarkers for the detection of Parkinson's disease.

Different protein structure

What makes this study special is that while the potential biomarker proteins are found in both healthy and diseased individuals, their molecules are present in different shapes (or structures) in each of the two groups. It is not the presence of certain proteins that indicates the disease, but rather the shape they have assumed. This is the first time that scientists have shown that an analysis of the structures of all proteins in a body fluid can identify potential biomarkers for disease.
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Biomarker in urine could be the first to reveal early-stage Alzheimer's disease
https://medicalxpress.com/news/2022-11- ... eimer.html
by Frontiers
Alzheimer's disease can remain undetected until it is too late to treat. Large-scale screening programs could help to detect early-stage disease, but current diagnostic methods are too cumbersome and expensive. Now, a new study is the first to identify formic acid as a sensitive urinary biomarker that can reveal early-stage Alzheimer's disease, potentially paving the way for inexpensive and convenient disease screening.

Could a simple urine test reveal if someone has early-stage Alzheimer's disease and could this pave the way for large-scale screening programs? A new study in Frontiers in Aging Neuroscience certainly suggests so. The researchers tested a large group of patients with Alzheimer's disease of different levels of severity and healthy controls with normal cognition to identify differences in urinary biomarkers.

They found that urinary formic acid is a sensitive marker of subjective cognitive decline that may indicate the very early stages of Alzheimer's disease. Current methods to diagnose Alzheimer's are expensive, inconvenient, and unsuitable for routine screening. This means that most patients only receive a diagnosis when it is too late for effective treatment. However, a non-invasive, inexpensive, and convenient urine test for formic acid could be just what the doctor ordered for early screening.

"Alzheimer's disease is a continuous and concealed chronic disease, meaning that it can develop and last for many years before obvious cognitive impairment emerges," said the authors. "The early stages of the disease occur before the irreversible dementia stage, and this is the golden window for intervention and treatment. Therefore, large-scale screening for early-stage Alzheimer's disease is necessary for the elderly."
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Drug slows Alzheimer's but can it make a real difference?
https://medicalxpress.com/news/2022-11- ... rence.html
by Lauran Neergaard
An experimental Alzheimer's drug modestly slowed the brain disease's inevitable worsening, researchers reported Tuesday—but it remains unclear how much difference that might make in people's lives.

Japanese drugmaker Eisai and its U.S. partner Biogen had announced earlier this fall that the drug lecanemab appeared to work, a badly needed bright spot after repeated disappointments in the quest for better Alzheimer's treatments.

Now the companies are providing full results of the study of nearly 1,800 people in the earliest stages of the mind-robbing disease. The data was presented at an Alzheimer's meeting in San Francisco and published in The New England Journal of Medicine. U.S. regulators could approve the drug as soon as January.
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Small studies of 40Hz sensory stimulation confirm safety, suggest Alzheimer's benefits
https://medicalxpress.com/news/2022-12- ... eimer.html
by Massachusetts Institute of Technology
Two early stage clinical studies testing the safety and efficacy of 40Hz sensory stimulation to treat Alzheimer's disease have found that the potential therapy was well tolerated, produced no serious adverse effects and was associated with some significant neurological and behavioral benefits among a small cohort of participants.

"In these clinical studies we were pleased to see that volunteers did not experience any safety issues and used our experimental light and sound devices in their homes consistently," said Li-Huei Tsai, Picower Professor in the The Picower Institute for Learning and Memory at MIT and senior author of the paper describing the studies in PLOS ONE Dec. 1. "While we are also encouraged to see some significant positive effects on the brain and behavior, we are interpreting them cautiously given our study's small sample size and brief duration. These results are not sufficient evidence of efficacy, but we believe they clearly support proceeding with more extensive study of 40Hz sensory stimulation as a potential non-invasive therapeutic for Alzheimer's disease."
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Short term memory problems can be improved with laser therapy, according to new study
https://medicalxpress.com/news/2022-12- ... laser.html
by University of Birmingham
Laser light therapy has been shown to be effective in improving short term memory in a study published in Science Advances.

Scientists at the University of Birmingham in the U.K. and Beijing Normal University in China, demonstrated that the therapy, which is non-invasive, could improve short term, or working memory in people by up to 25%.

The treatment, called transcranial photobiomodulation (tPBM), is applied to an area of the brain known as the right prefrontal cortex. This area is widely recognized as important for working memory. In their experiment, the team showed how working memory improved among research participants after several minutes of treatment. They were also able to track the changes in brain activity using electroencephalogram (EEG) monitoring during treatment and testing.
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Droplets in cells found to determine the accumulation of proteins in age-related diseases
https://phys.org/news/2022-12-droplets- ... lated.html
by Radboud University
Tiny droplets in cells can accelerate the accumulation of protein deposits in diseases such as Alzheimer's and Parkinson's disease, but they can also hinder this accumulation. While they will worsen the accumulation if the proteins stick to the edge of the droplets, the situation actually improves when they are incorporated into the droplets. Chemists from Radboud University and the University of Twente are set to publish their new findings in Science Advances on December 2.

Molecules do not just bob around inside our cells. We know for about a decade now that many molecules form tiny droplets in our cells. These droplets are formed by a chemical process called phase separation. "It's just like oil in water," explains researcher Brent Visser. "The only difference is that these droplets usually consist of a complex mix of large molecules that are found in the cell, such as RNA and proteins."

Without these droplets, our cells would not work. They ensure that the molecules can converge in the right place. But scientists do not yet know whether cells can actually control this process or whether the droplets have an impact on disease development.
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