The Brain: Alzheimer's and dementia news and discussions

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When Alzheimer's degrades cells that cross hemispheres, visual memory suffers
https://medicalxpress.com/news/2022-08- ... isual.html
by Massachusetts Institute of Technology

A new MIT study finds that Alzheimer's disease disrupts at least one form of visual memory by degrading a newly identified circuit that connects the vision processing centers of each brain hemisphere.

The results of the study, published in Neuron by a research team based at The Picower Institute for Learning and Memory, come from experiments in mice, but provide a physiological and mechanistic basis for prior observations in human patients: the degree of diminished brain rhythm synchrony between counterpart regions in each hemisphere correlates with the clinical severity of dementia.

"We demonstrate that there is a functional circuit that can explain this phenomenon," said lead author Chinnakkaruppan Adaikkan, a former Picower Institute postdoc who is now an assistant professor in the Center for Brain Research at the Indian Institute of Science (IISc) in Bangalore. "In a way we uncovered a fundamental biology that was not known before."

Specifically, Adaikkan's work identified neurons that connect the primary visual cortex (V1) of each hemisphere and showed that when the cells are disrupted, either by genetic alterations that model Alzheimer's disease or by direct laboratory perturbations, brain rhythm synchrony becomes reduced and mice become significantly less able to notice when a new pattern appeared on a wall in their enclosures. Such recognition of novelty, which requires visual memory of what was there the prior day, is an ability commonly disrupted in Alzheimer's.
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Neuron membrane lipid may contribute to Alzheimer's development, progression
https://medicalxpress.com/news/2022-08- ... eimer.html
by Zach Sweger, Pennsylvania State University
A lipid found in the membranes of neurons may play a fundamental role in the development and progression of Alzheimer's disease, according to a study by Penn State College of Medicine researchers. Their findings, published in ACS Chemical Neuroscience, provide possibilities for new approaches to pharmaceutical research on Alzheimer's disease.

Alzheimer's disease is a common neurodegenerative disorder, responsible for 60% to 70% of dementia cases. The economic burden associated with caring for nearly 50 million people worldwide with the condition is annually estimated to be in the hundreds of billions of dollars. Researchers are seeking to better understand how the disease forms and progresses so new therapeutics can be developed for treatment.

A research team led by Nikolay Dokholyan, G. Thomas Passananti Professor and vice chair for research in the Department of Pharmacology, investigated how monosialotetrahexosylganglioside (GM1)—a molecule found in cell membranes—contributes to the formation of toxic oligomers, or harmful protein clusters, consisting of a protein called amyloid beta (Aβ). This protein aggregation has been associated with the development and progression of Alzheimer's disease.
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Artificial intelligence model can detect Parkinson's from breathing patterns
https://medicalxpress.com/news/2022-08- ... terns.html
by Alex Ouyang, Massachusetts Institute of Technology
Parkinson's disease is notoriously difficult to diagnose as it relies primarily on the appearance of motor symptoms such as tremors, stiffness, and slowness, but these symptoms often appear several years after the disease onset. Now, Dina Katabi, the Thuan (1990) and Nicole Pham Professor in the Department of Electrical Engineering and Computer Science (EECS) at MIT and principal investigator at MIT Jameel Clinic, and her team have developed an artificial intelligence model that can detect Parkinson's just from reading a person's breathing patterns.

The tool in question is a neural network, a series of connected algorithms that mimic the way a human brain works, capable of assessing whether someone has Parkinson's from their nocturnal breathing—i.e., breathing patterns that occur while sleeping. The neural network, which was trained by MIT Ph.D. student Yuzhe Yang and postdoc Yuan Yuan, is also able to discern the severity of someone's Parkinson's disease and track the progression of their disease over time.

Yang and Yuan are co-first authors on a new paper describing the work, published today in Nature Medicine. Katabi, who is also an affiliate of the MIT Computer Science and Artificial Intelligence Laboratory and director of the Center for Wireless Networks and Mobile Computing, is the senior author. They are joined by 12 colleagues from Rutgers University, the University of Rochester Medical Center, the Mayo Clinic, Massachusetts General Hospital, and the Boston University College of Health and Rehabilition.
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In trial, brain zaps gave seniors a month-long memory boost
https://medicalxpress.com/news/2022-08- ... niors.html
by Denise Mann
If you're a senior who struggles to remember where you put your car keys, could noninvasive brain stimulation boost your memory?

Yes, claims a new study that found folks who were treated with transcranial alternating current stimulation for four days in a row showed greater improvements in their ability to recall things than people who underwent a sham procedure. The effect seemed to last for weeks.

"The effects were moderate to large, and an overwhelming majority of people experienced the memory improvements," study author Robert Reinhart said during a recent media briefing on the findings. Reinhart is the director of the Cognitive & Clinical Neuroscience Laboratory at Boston University.

For the study, 150 adults aged 65 to 88 received treatment targeting their short-term memory, long-term memory, or a placebo procedure. Most were experiencing normal age-related declines in memory. No one in the study had been diagnosed with Alzheimer's disease.

Participants in the active treatment groups wore a shower cap with embedded electrodes that was hooked up to a brain stimulation device that emits weak electrical currents via the electrodes. Each session lasted 20 minutes, and folks were asked to listen to and then immediately recall five lists of 20 words during treatment.
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Do WTC responders with cognitive impairment show signs of a new form of dementia?
https://medicalxpress.com/news/2022-08- ... entia.html
by Stony Brook University
A study that assessed the brains of 99 World Trade Center (WTC) responders by using diffusion tractography, a 3D imaging technique, showed that WTC responders with cognitive impairment (CI), a possible sign of dementia, and post-traumatic stress disorder (PTSD), have a different presentation of the white matter in their brains compared to responders with CI without PTSD. Led by researchers at Stony Brook University affiliated with the Stony Brook WTC Health and Wellness Program, the study suggests a specific form of dementia could be affecting WTC responders who also have PTSD. The findings are published early online in the Journal of Alzheimer's Disease.

According to the authors, this is the first study to examine white matter alterations using connectometry in a sample of WTC responders in mid-life (average age: 56) with and without concurrent PTSD. The goal of the study was to examine and elucidate the extent to which white matter tract integrity might be impaired in WTC responders with CI and/or PTSD. Previously, the researchers had identified changes in white matter diffusivity in small numbers of responder patients.

"Our findings are by no means conclusive in terms of defining CI or dementia in WTC responders, and if this study provides evidence of a new form of dementia emerging," says Sean Clouston, Ph.D., lead author and Associate Professor in the Program in Public Health, and in the Department of Family, Population, and Preventive Medicine at Stony Brook University.
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Researchers uncover where and why proteins malfunction in Parkinson's disease

by The Francis Crick Institute

Scientists at the Francis Crick Institute, UCL and the University of Edinburgh have uncovered how a build-up of harmful protein starts to happen within neurons in Parkinson's disease, ultimately causing nerve cell death. By looking at how, where and why this build-up happens, the work provides unique insight into a key biological process driving Parkinson's.

Parkinson's is a progressive neurodegenerative disease that causes tremors, slowing of movements, stiffness and can progress to cause severe cognitive problems. It affects around 145,000 people in the UK, with this number expected to increase as more people live longer.

Parkinson's is caused by a loss of neurons in specific parts of the brain. In affected nerve cells, a protein called alpha-synuclein misfolds and clumps together into harmful structures. The mechanisms behind this are not yet fully understood.

In their paper, published in Nature Neuroscience today, the researchers developed a new sensitive approach to study what happens to alpha-synuclein during the earliest stages of disease.
https://medicalxpress.com/news/2022-08- ... sease.html
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Brain's support cells may hold key to new Huntington's treatments
https://medicalxpress.com/news/2022-08- ... ments.html
by University of Rochester Medical Center

Huntington's disease—a hereditary and fatal genetic disorder—has long been considered a neuronal disease due to the permanent loss of medium spiny motor neurons, the death of which over time is responsible for the clinical hallmarks of the disease: involuntary movements, problems with coordination, cognitive decline, depression, and psychosis.

However, a growing body of research, including a new study appearing in the journal Cell Reports, suggests that the disease may also flow from defects in glia, important support cells found in the brain. The new study expands our understanding of the underlying mechanisms of the disease, and reinforces the potential of therapies that target glia cells.
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3D imaging helps to better understand the early stages of Alzheimer's disease
https://medicalxpress.com/news/2022-08- ... eimer.html
by Karolinska Institutet
Using a novel 3D imaging technology, researchers at Karolinska Institutet, among others, have been able to comprehensively characterize a part of the brain that shows perhaps the earliest accumulation of tau protein, an important biomarker for the development of Alzheimer's disease. The results, published in the journal Acta Neuropathologica, may make it possible in the future to have a more precise neuropathological diagnosis of the Alzheimer's disease spectrum at a very early stage.

Intracellular accumulation of pathological tau protein in the brain is a hallmark of several age-related neurodegenerative disorders, including Alzheimer's disease, which accounts for 60–80% of all dementia cases worldwide.

In a new study, researchers at Karolinska Institutet, SciLifeLab in Stockholm and several universities from Hungary, Canada, Germany and France applied a state-of-the-art volume immuno-imaging technology, in combination with light sheet microscopy, to investigate a human brainstem nucleus called locus coeruleus, which is a key hub in the mammalian brain.
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New antibody shows therapeutic effects in mice with Alzheimer's disease
https://medicalxpress.com/news/2022-09- ... eimer.html
by University of Texas Health Science Center at Houston

A newly developed agonistic antibody reduced the amyloid pathology in mice with Alzheimer's disease, signaling its promise as a potential treatment for the disease, according to a team of researchers at UTHealth Houston.

Research led by senior author Zhiqiang An, Ph.D., professor and Robert A. Welch Distinguished University Chair in Chemistry at McGovern Medical School at UTHealth Houston, found that a tetra-variable domain antibody targeting the triggering receptor expressed on myeloid 2 (TREM2)—dubbed TREM2 TVD-lg—reduced amyloid burden, eased neuron damage, and alleviated cognitive decline in mice with Alzheimer's disease. The study was published today in Science Translational Medicine.

"Antibody-based therapy is a viable drug modality for the treatment of Alzheimer's disease," said An, director of the Texas Therapeutics Institute with The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases (IMM). "One of the major areas of focus at the Texas Therapeutics Institute is developing technologies to deliver antibody-based therapies across the blood-brain barrier for potential treatment of the disease."

TREM2 is a single-pass receptor expressed by microglia—supportive cells that function as scavengers in the central nervous system. Microglia play a crucial role in the removal of amyloids that cluster around amyloid-beta plaques, a hallmark of Alzheimer's disease.

While previous research has shown that TREM2 plays an important role in the pathophysiology of Alzheimer's disease, the recent findings suggest that increasing TREM2 activation could have therapeutic effects such as improved cognition.
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Parkinson's breakthrough can diagnose disease from skin swabs in three minutes
https://medicalxpress.com/news/2022-09- ... swabs.html
by Ben Robinson, University of Manchester
A new method to detect Parkinson's disease has been determined by analyzing sebum with mass spectrometry.

The study, published today in the JACS Au , have found that there are lipids of high molecular weight that are substantially more active in people suffering from Parkinson's disease.

The researchers from The University of Manchester used cotton swabs to sample people and identify the compounds present with mass spectrometry. The method developed involves paper spray ionization mass spectrometry combined with ion mobility separation and can be performed in as little as three minutes from swab to results.

Professor Perdita Barran at The University of Manchester, who led the research said, "We are tremendously excited by these results which take us closer to making a diagnostic test for Parkinson's Disease that could be used in clinic."

The research used a sample group of 79 people with Parkinson's compared with a heathy control group of 71 people.

The study has arisen from the observation of Joy Milne, who discovered that she can distinguish PD in individuals from a distinct body odor before clinical symptoms occur.

Joy has hereditary Hyperosmia—a heightened sensitivity to smells—which has been exploited to find that Parkinson's has a distinct odor which is strongest where sebum collects on patient's backs and is less often washed away.
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