Alzheimer's and dementia news and discussions

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Alzheimer's and dementia news and discussions

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Protein linked to heart health, disease a potential therapeutic target for dementia
https://medicalxpress.com/news/2021-06- ... sease.html
by Washington University School of Medicine
By the time people with Alzheimer's disease start exhibiting difficulty remembering and thinking, the disease has been developing in their brains for two decades or more, and their brain tissue already has sustained damage. As the disease progresses, the damage accumulates, and their symptoms worsen.

Researchers at Washington University School of Medicine in St. Louis have found that high levels of a normal protein associated with reduced heart disease also protect against Alzheimer's-like brain damage—at least in mice. The findings, published June 21 in Neuron, suggest that raising levels of the protein—known as low-density lipoprotein receptor (LDL receptor)—could potentially be a way to slow or stop cognitive decline.
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Investigational Alzheimer's drug improves biomarkers of the disease

by Washington University School of Medicine
https://medicalxpress.com/news/2021-06- ... sease.html
An investigational Alzheimer's drug reduced molecular markers of disease and curbed neurodegeneration in the brain, without demonstrating evidence of cognitive benefit, in a phase 2/3 clinical trial led by researchers at Washington University School of Medicine in St. Louis through its Dominantly Inherited Alzheimer Network-Trials Unit (DIAN-TU). These results led the trial leaders to offer the drug, known as gantenerumab, to participants as part of an exploratory open-label extension. The researchers continue to monitor changes in measures of Alzheimer's disease in those participants who are receiving the drug.

The DIAN-TU study (ClinicalTrials.gov Identifier: NCT01760005), published June 21 in Nature Medicine, evaluated the effects of two investigational drugs—gantenerumab, made by Roche and its U.S. affiliate, Genentech, and solanezumab, made by Eli Lilly and Co.—in people with a rare, inherited, early-onset form of Alzheimer's known as dominantly inherited Alzheimer's disease or autosomal dominant Alzheimer's disease. Such people are born with a mutation that causes Alzheimer's, and experience declines in memory and thinking skills starting as early as their 30s or 40s.
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Brain cell membranes' lipids may play big role in Alzheimer's progression
https://medicalxpress.com/news/2021-06- ... s-big.html
by American Institute of Physics
Alzheimer's disease is predominant in elderly people, but the way age-related changes to lipid composition affect the regulation of biological processes is still not well understood. Links between lipid imbalance and disease have been established, in which lipid changes increase the formation of amyloid plaques, a hallmark of Alzheimer's disease.

This imbalance inspired researchers from Aarhus University in Denmark to explore the role of lipids comprising the cellular membranes of brain cells.

In Biointerphases, the researchers report on the significant role lipids may play in regulating C99, a protein within the amyloid pathway, and disease progression. Lipids have been mostly overlooked from a therapeutic standpoint, likely because their influence in biological function is not yet fully understood.
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Discovery of nanosized molecules that might inhibit Alzheimer's and Parkinson's diseases
https://phys.org/news/2021-07-discovery ... eimer.html
by Umea University

Nanosized molecules of a particular chemical element can inhibit the formation of plaque in the brain tissues. This new discovery by researchers at Umeå University, Sweden, in collaboration with researchers in Croatia and Lithuania, provides renewed hope for novel treatments of, for instance, Alzheimer's and Parkinson's disease in the long run.

"This is indeed a very important step that may form the basis of new and efficient treatments of neurodegenerative diseases in the future," says Professor Ludmilla Morozova-Roche at Umeå University.

When proteins misfold they form insoluble fibrils called amyloids, which are involved in several serious diseases such as Alzheimer's and Parkinson's, Corino de Andrade's and the mad cow disease. Amyloid aggregates kill neuronal cells and form amyloid plaques in the brain tissues.

What researchers in Umeå in Sweden, Vilnius in Lithuania and Rijeka in Croatia have discovered is that a particular nanosized molecules can hinder the amyloid formation of pro-inflammatory protein S100A9. These molecules are able even to dissolve already pre-formed amyloids, which has been shown by using atomic force microscopy and fluorescence techniques. The molecules in question are nanosized polyoxoniobates, which is so-called polyoxometalate ions with a negative charge containing the chemical element niobium.
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Excess coffee use shown to decrease brain volume, increase dementia risk

by University of South Australia
https://medicalxpress.com/news/2021-07- ... brain.html
It's a favorite first-order for the day, but while a quick coffee may perk us up, new research from the University of South Australia shows that too much could be dragging us down, especially when it comes to brain health.

In the largest study of its kind, researchers have found that high coffee consumption is associated with smaller total brain volumes and an increased risk of dementia.

Conducted at UniSA's Australian Centre for Precision Health at SAHMRI and a team of international researchers, the study assessed the effects of coffee on the brain among 17,702 UK Biobank participants (aged 37-73), finding that those who drank more than six cups of coffee a day had a 53 per cent increased risk of dementia.
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Key brain region involved in more than locomotion, finding may improve Parkinson's treatments

by Friedrich Miescher Institute for Biomedical Research
https://medicalxpress.com/news/2021-07- ... otion.html
For decades, a key brain area called the mesencephalic locomotor region has been thought to merely regulate locomotion. Now, researchers in Silvia Arber's group have shown that the region is involved in much more than walking, as it contains distinct populations of neurons that control different body movements. The findings could help to improve certain therapies for Parkinson's disease, a neurodegenerative condition that leads to tremor, stiffness, and problems controlling different movements.

Even the mundane act of walking requires complex movements such as postural changes and the coordination of all four limbs. Scientists have known that the mesencephalic locomotor region, which is part of the midbrain, is involved in regulating walking and other forms of locomotion in many animal species. But the function of neurons in this area of the brain remained controversial.
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Brain cholesterol regulates Alzheimer's plaques, study reveals
https://medicalxpress.com/news/2021-08- ... veals.html
by The Scripps Research Institute

A team co-led by scientists at Scripps Research has used advanced imaging methods to reveal how the production of the Alzheimer's-associated protein amyloid beta (Aβ) in the brain is tightly regulated by cholesterol.

Appearing on line Thursday ahead of print in the Aug. 17 issue of the Proceedings of the National Academy of Sciences (PNAS), the scientists' work advances understanding of how Alzheimer's disease develops and underscores the long-underappreciated role of brain cholesterol. The findings also help explain why genetic studies link Alzheimer's risk to a cholesterol-transporting protein called apolipoprotein E (apoE).

"We showed that cholesterol is acting essentially as a signal in neurons that determines how much Aβ gets made—and thus it should be unsurprising that apoE, which carries the cholesterol to neurons, influences Alzheimer's risk," says study co-senior author Scott Hansen, Ph.D., an associate professor in the Department of Molecular Medicine at Scripps Research, Florida.
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Brain tissue inflammation is key to Alzheimer's disease progression
https://medicalxpress.com/news/2021-08- ... eimer.html
by University of Pittsburgh
Neuroinflammation is the key driver of the spread of pathologically misfolded proteins in the brain and causes cognitive impairment in patients with Alzheimer's disease, researchers from the University of Pittsburgh School of Medicine reveal in a paper published today in Nature Medicine.

For the first time ever, the researchers showed in living patients that neuroinflammation—or activation of the brain's resident immune cells, called microglial cells—is not merely a consequence of disease progression; rather, it is a key upstream mechanism that is indispensable for disease development.

"As a young resident neurologist in my home country of Brazil, I noticed that many patients with Alzheimer's disease are left neglected and without access to appropriate care," said lead author Tharick Pascoal, M.D., Ph.D., assistant professor of psychiatry and neurology at Pitt. "Our research suggests that combination therapy aimed to reduce amyloid plaque formation and limit neuroinflammation might be more effective than addressing each pathology individually."
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Stem cells model genetic risk for developing Alzheimer's disease
https://medicalxpress.com/news/2021-08- ... sease.html
New research published in Stem Cell Reports has found elevated cholesterol supply from astrocytes to neurons in the model of Alzheimer's disease (AD) brains, suggesting that modulating brain cholesterol could be explored in the search of treatment options for the devastating, degenerative disease.

AD, the most frequent cause of dementia, affects an estimated 24 million people worldwide. With very limited treatment options, scientists are looking for ways to understand the disease better. One hallmark of AD is the emergence of so-called beta-amyloid plaques, clumps of beta-amyloid protein accumulating in the brain and thought to be toxic to adjacent neurons. The causes for Alzheimer's disease and the formation of beta-amyloid plaques are still largely unknown but genetic studies found that a gene called APOE, which is involved in cholesterol metabolism and transport, is linked to AD in the elderly. The APOE gene exists in different versions in people, APOE2, APOE3 and APOE4, but the APO4 gene comes with a relatively higher risk of developing AD.
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Restoring 'chaperone' protein may prevent plaque build-up in Alzheimer's
https://medicalxpress.com/news/2021-08- ... eimer.html
by Perelman School of Medicine at the University of Pennsylvania

For the first time, Penn Medicine researchers showed how restoring levels of the protein DAXX and a large group of similar proteins prevents the misfolding of the rogue proteins known to drive Alzheimer's and other neurodegenerative diseases, as well as certain mutations that contribute to cancers. The findings could lead to new targeted approaches that would restore a biological system designed to keep key proteins in check and prevent diseases.

The findings were published online in Nature.

The study focuses on DAXX, or death domain-associated protein, which is a member of a large family of human proteins, each with an unusually high content of two specific amino acid residues, aspartate and glutamate, referred to as polyD/E proteins. The various roles of DAXX and approximately 50 other polyD/E proteins in cell processes have emerged over time,
but their role as a protein quality control system—a "chaperone" that directs protein folding, so to speak—was unanticipated.
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