The Brain: Alzheimer's and dementia news and discussions

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Molecule found in seafood plays role in protecting and improving cognitive function
https://medicalxpress.com/news/2021-12- ... ction.html
by Nottingham Trent University
Research at Nottingham Trent University and Queen Mary University of London investigated the role of trimethylamine N-oxide (TMAO) a molecule which is present in people's diets and produced by the body during digestion of fish.

Alzheimer's Research UK funded the study, which adds to a growing body of work aiming to understand and demonstrate how bacteria in the gut and the molecules they interact with influence human health and disease.

As foods containing TMAO are ingested, the molecule is broken down by bacteria in the gut. The breakdown product is taken up into the bloodstream and converted back to TMAO, which interacts with organs throughout the body.

Importantly, the brain's circulatory and vascular system is exposed to TMAO, which interacts directly with the 'blood-brain barrier." This barrier works to prevent potentially harmful toxins in the body from reaching the brain.
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Head-mounted microscope allows long-term brain imaging in freely moving mice

by The Optical Society
https://medicalxpress.com/news/2021-12- ... aging.html
Researchers have developed the first detachable head-mounted photoacoustic microscope for imaging brain activity in freely moving mice. Because the device can be removed after imaging, it enables long-term studies that could reveal important new insights into neurodegenerative diseases and other neurological disorders.

"Epilepsy, Alzheimer's disease and Parkinson's disease can all seriously interrupt neurovascular coupling—the link between neural activity and subsequent changes in cerebral blood flow," said research team leader Lei Xi from the Southern University of Science and Technology in China. "Our new probe is ideal for studying neurovascular coupling because it has the potential to capture the dynamics of both neuron and vascular networks simultaneously."

The new microscope probe weighs just 1.8 grams and is based on optical resolution photoacoustic microscopy (ORPAM), which can capture anatomical and functional dynamics of the brain without requiring the use of fluorescent tags or labels. In the Optica Publishing Group journal Optics Letters, Xi and colleagues describe how they optimized the design of the new probe to make it light enough for use in freely moving mice.

"Head-mounted microscopes that use multi-photon or fluorescence imaging primarily capture the activities of single neurons," said Xi. "Our ORPAM probe can capture cerebral vascular network and hemodynamics of large portions of the cerebral cortex with capillary-level resolution without requiring any labels."

Miniaturizing a microscope

The new work builds on a wearable ORPAM probe the researchers previously built for freely moving rats. Although it performed well, it had to be permanently fixed on the rat and was too large and heavy to be carried around by mice, which are the preferred animal models for many brain studies.
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Are scientists homing in on a cure for Parkinson's disease?
https://medicalxpress.com/news/2021-12- ... sease.html
by University of Bath
A molecule that shows promise in preventing Parkinson's disease has been refined by scientists at the University of Bath in the UK, and has the potential to be developed into a drug to treat the deadly neurodegenerative disease.

Professor Jody Mason, who led the research from the Department of Biology and Biochemistry at Bath, said: "A lot of work still needs to happen, but this molecule has the potential to be a pre-cursor to a drug. Today there are only medicines to treat the symptoms of Parkinson's—we hope to develop a drug that can return people to good health even before symptoms develop."

Parkinson's Disease is characterized by a specific protein in human cells 'misfolding', where it becomes aggregated and malfunctions. The protein—alpha-synuclein (αS) – is abundant in all human brains. After misfolding, it accumulates in large masses, known as Lewy bodies. These masses consist of αS aggregates that are toxic to dopamine-producing brain cells, causing them to die. It is this drop in dopamine signaling that triggers the symptoms of Parkinson's Disease, as the signals transmitting from the brain to the body become noisy, leading to the distinctive tremors seen in sufferers.
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Wear and tear in vulnerable brain areas lead to lesions linked to cognitive decline
https://medicalxpress.com/news/2021-12- ... inked.html
by Stevens Institute of Technology

As our brains age, small lesions begin to pop up in the bundles of white matter that carry messages between our neurons. The lesions can damage this white matter and lead to cognitive deficits. Now, researchers at Stevens Institute of Technology and colleagues not only provide an explanation for the location of these lesions but also how they develop in the first place.

The work, led by Johannes Weickenmeier, an assistant professor of mechanical engineering at Stevens, highlights the importance of viewing the brain as more than neural circuitry that underpins how thoughts are formed, and memories created. It's also a physical object that's prone to glitches and mechanical failures. "The brain is susceptible to wear and tear in vulnerable areas," Weickenmeier said. "Especially in an aging brain, we need to look at its biomechanical properties to better understand how things can start to go wrong.'

These lesions—known as deep and periventricular white matter hyperintensities because they show up as bright white patches on MRI scans—are poorly understood. But they are not uncommon: most people have some by the time they reach their 60s, and changes only increase with age. The more lesions that accumulate and the faster they grow, the more prone we become to cognitive impairments ranging from memory problems to motor disorders.

Using MRI scans from eight healthy subjects, Weickenmeier worked with Valery Visser, now a doctorate student at the University of Zurich, and Henry Rusinek, a radiologist at NYU Grossman School of Medicine, to develop an individualized computer model of each subject's brain. The team mapped the strain placed on ventricular walls, the linings of fluid-filled chambers deep in the brain, as waves of pressure pulse through the subject's cerebral spinal fluid, or CSF. They found that hyperintensities tend to occur near areas that must stretch more to accommodate pressure changes of the circulating CSF because, as such areas wear thin, CSF can leak into the brain and cause lesions.
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Twins study indicates environmental factors significant in Alzheimer's pathology
https://medicalxpress.com/news/2021-12- ... eimer.html
by CHeBA

The question of genetic vs environmental influences plays a major role in research into brain aging, with researchers from UNSW Sydney's Centre for Healthy Brain Aging (CHeBA) revealing new insights into one of the hallmarks of Alzheimer's disease—amyloid plaques—by looking at the brains of identical and non-identical twins.

The world first study, led by Dr. Rebecca Koncz and published in the Journal of Neurology, Neurosurgery & Psychiatry, used a special type of imaging called amyloid PET, or 'position emission tomography' to determine what proportion of amyloid accumulation is determined by genes, and what proportion is determined by environmental, or modifiable risk factors such as high blood pressure and high cholesterol.

"Amyloid is a protein that accumulates in the brain very early in the development of Alzheimer's disease," said Dr. Koncz. "It is a hallmark feature of the condition that starts to accumulate decades before memory problems become apparent."

According to Professor Perminder Sachdev, co-director of CHeBA and leader of the Older Australian Twins Study, twins provide a unique opportunity to investigate the relative importance of genetic and lifestyle factors for Alzheimer's disease, because monozygotic twins share 100 percent of their genetic material, and dizygotic twins share an estimated 50 percent. Australia has one of the world's leading twin registries—Twin Research Australia—members of which participated in the study. The amyloid PET imaging was done in collaboration with the Department of Molecular Imaging and Therapy, Austin Hospital, Melbourne, and the Department of Nuclear Medicine and PET at Prince of Wales Hospital in Sydney.
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Biogen Quickly Cuts Alzheimer's Drug Cost After Payer Pushback
Source: Bloomberg
(Bloomberg) -- Biogen Inc. said it would cut the list price of its Alzheimer’s disease drug Aduhelm in half in the U.S., a move that comes after the treatment’s high cost spurred concerns that it could strain Medicare and health insurers.

The company said in a statement on Monday that it would reduce the annual list price of the treatment to $28,200 to lower out-of-pocket costs for patients and reduce “the potential financial implications for the U.S. health-care system.”

It is unusual for pharmaceutical companies to drastically reduce the cost of a medication soon after it is approved. Aduhelm won backing from the Food and Drug Administration in June, becoming the first new drug for Alzheimer’s in nearly 20 years. The memory-wasting disease affects some 6 million Americans, most of them elderly.

However, the treatment has faced skepticism from doctors and medical experts who aren’t certain that it works and from payers who viewed its $56,000-a-year cost as prohibitive. Private insurers say they need more evidence that Aduhelm actually slows the rate at which Alzheimer’s patients deteriorate. Last month, none of the 25 large insurers that responded to a Bloomberg News survey said that they found the drug to be “medically necessary.”
Read more: https://www.msn.com/en-us/money/other/b ... ar-AARZbJj
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Neuroprotective mechanism altered by Alzheimer's disease risk genes
https://medicalxpress.com/news/2021-12- ... genes.html
by Molly Chiu, Baylor College of Medicine

The brain has a natural protective mechanism against Alzheimer's disease, and researchers at Baylor College of Medicine, Texas Children's Hospital and collaborating institutions have discovered that gene variants associated with risk of developing the disease disturb the protective mechanism in ways that can lead to neurodegeneration. The researchers also showed in a fruit fly model of the condition that a chemical known as ABCA1 agonist can restore certain alterations of the brain protective mechanism.

The team reveals evidence supporting reactive oxygen species (ROS), natural byproducts of cellular metabolism linked to inflammation and other processes, as key players in events leading to the disruption of the neuroprotective mechanism. In addition, the researchers found that ROS, together with amyloid-beta, the main component in the plaques found in the brains of people with Alzheimer's disease, accelerated disease development in animal models. Altogether, the findings provide new mechanistic insight into factors involved in Alzheimer's disease development, supporting the idea that multiple alterations at the genetic and other cellular levels combine to induce the disease. The study appears in the Proceedings of the National Academy of Sciences.
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Findings open the way to more precise diagnoses and treatments of Alzheimer's disease
https://medicalxpress.com/news/2022-01- ... sease.html
by Case Western Reserve University

An international team led by Case Western Reserve University's School of Medicine has made a significant breakthrough in understanding why Alzheimer's disease progresses so rapidly in some people that they die within three years.

The researchers found a link between strains of misshapen and fast-replicating tau protein and accelerated cognitive decline—a critical result that illuminates the variations in Alzheimer's disease and could help lead to more precise diagnoses and targeted therapies.

Such work could lead to changes in Alzheimer's care, possibly giving patients and families more accurate prognoses.

"For the first time, we established the link between the behavior of tau protein in the test tube and the clinical duration of the disease in patients," said Jiri Safar, a professor in the departments of pathology, neurology, and neurosciences at the Case Western Reserve School of Medicine. "What the research says in general is that Alzheimer's is not a single disease. There is a spectrum, and different cases have distinct biological drivers of the progression—and they should be handled as separate diseases."
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Flavonoids may reduce mortality risk for people with Parkinson's disease
https://medicalxpress.com/news/2022-01- ... sease.html
by Pennsylvania State University

People with Parkinson's disease who eat more flavonoids—compounds found in richly colored foods like berries, cocoa and red wine—may have a lower mortality risk than those who don't, according to a new study.

Specifically, the researchers found that when people who had already been diagnosed with Parkinson's disease (PD) ate more flavonoids, they had a lower chance of dying during the 34-year study period than those who did not consume as many flavonoids.

Additionally, they found that eating more flavonoids before being diagnosed with PD was associated with a lower risk of dying in men, but not in women.
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A protein present in the gums may help prevent Alzheimer's
https://medicalxpress.com/news/2022-02- ... eimer.html
by Béatrice St-Cyr-Leroux, University of Montreal

A research team affiliated with the Faculty of Dentistry at the University of Montreal has shed new light on a human protein with potential benefits beyond oral and dental health.

Recent studies have shown that a protein present in the gingival epithelium (the part of the gums that surrounds the teeth) may have antimicrobial properties, in particular against the bacterium Porphyromonas gingivalis (P. gingivalis). In addition to playing a significant role in periodontal disease, this bacterium may also be linked to neurodegenerative diseases such as Alzheimer's.

The findings of the study led by Antonio Nanci, a researcher and professor in the Department of Stomatology at the University of Montreal, and postdoctoral researcher Charline Mary, in collaboration with colleagues from Université Laval and McGill University, were recently published in the journal Scientific Reports.

The study sheds new light on secretory calcium-binding phosphoprotein proline-glutamine rich 1 (SCPPPQ1), a protein expressed by the cells of the junctional epithelium. The findings suggest that this protein has antibacterial potential and identify its active portions.
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