The Brain: Alzheimer's and dementia news and discussions

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Eli Lilly Alzheimer’s treatment donanemab slowed disease progression in clinical trial
Published Wed, May 3 20236:00 AM EDTUpdated 4 Hours Ago
https://www.cnbc.com/2023/05/03/alzheim ... ssion.html

The Alzheimer’s treatment donanemab, which is made by Eli Lilly

, significantly slowed progression of the mind-robbing disease, according to clinical trial data released Wednesday by the company.

Patients who received the monthly antibody infusion during an 18-month study demonstrated a 35% slower decline in memory, thinking and their ability to perform daily activities compared with those who did not receive the treatment, Eli Lilly’s data showed.

Patients who took donanemab were 39% less likely to progress to the next stage of the disease during the study, according to the trial results.

But the treatment’s benefits will have to be weighed against the risk of brain swelling and bleeding that can be serious and even fatal in rare cases. Three participants in the trial died from these side effects.

Eli Lilly’s stock was up more than 6% in premarket trading Wednesday.

Lilly plans to apply for Food and Drug Administration approval of donanemab as soon as this quarter, according to the company. The trial studied individuals in the early stages of Alzheimer’s who had a confirmed presence of brain plaque associated with the disease.

Dr. Daniel Skovronsky, Lilly’s chief scientific and medical officer, said donanemab demonstrated the highest level of efficacy of any Alzheimer’s treatment in a clinical trial. The company is working to get donanemab approved and on the market as quickly as possible, he said.

And Skovronsky believes the FDA feel
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New Parkinson's test will unlock the disease's secrets
The new test is remarkably accurate (this is especially rare in brain disease). It will allow scientists to unlock some of Parkinson’s deepest-held secrets — like how early cellular dysfunction begins in brain and body cells, what other aspects of biology are involved in risk, onset and progression, and why Parkinson’s symptoms and disease course are so notoriously different in different people. This will crack wide open our ability to develop next-generation drugs that will benefit everyone living with the disease.
https://www.usatoday.com/story/opinion/ ... 169010007/
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Novel technique for rapid detection of neurodegenerative diseases like Parkinson's and chronic wasting disease

by University of Minnesota
https://phys.org/news/2023-05-technique ... inson.html
University of Minnesota Twin Cities researchers have developed a new diagnostic technique that will allow for faster and more accurate detection of neurodegenerative diseases. The method will likely open a door for earlier treatment and mitigation of various diseases that affect humans, such as Alzheimer's and Parkinson's, and similar diseases that affect animals, such as chronic wasting disease (CWD).

Their new study is published in Nano Letters.

"This paper mainly focuses on chronic wasting disease in deer, but ultimately our goal is to expand the technology for a broad spectrum of neurodegenerative diseases, Alzheimer's and Parkinson's being the two main targets," said Sang-Hyun Oh, senior co-author of the paper and a Distinguished McKnight University Professor in the University of Minnesota Department of Electrical and Computer Engineering.

"Our vision is to develop ultra-sensitive, powerful diagnostic techniques for a variety of neurodegenerative diseases so that we can detect biomarkers early on, perhaps allowing more time for the deployment of therapeutic agents that can slow down the disease progression. We want to help improve the lives of millions of people affected by neurodegenerative diseases."
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Gut bacteria linked to Parkinson's, paves way for targeted treatment
By Paul McClure
May 07, 2023
https://newatlas.com/medical/gut-bacter ... treatment/


A new study has found that a species of gut bacteria cause the destructive nerve cell ‘clumps’ that are a hallmark of Parkinson’s disease. The discovery opens the door to the development of targeted treatments for this debilitating disease.

More than 10 million people worldwide live with Parkinson’s disease (PD), an incurable neurodegenerative disorder characterized by tremors, muscle stiffness, hindered movement, and impaired balance and coordination.

When the protein alpha-synuclein (alpha-syn), predominantly found in nerve cells, clumps together, it forms Lewy bodies. The presence of alpha-syn/Lewy bodies in the brain and throughout the nervous system is a hallmark of PD. Clumped alpha-syn has also been found in the gut, and it’s thought that a gut-based pathogen may cause the aggregation, which then travels to the brain.
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First map of "Commander complex" could help fight diseases, dementia
By Michael Franco
May 12, 2023
https://newatlas.com/medical/map-commander-complex/
Using AI, researchers have created the first map of a group of proteins known as the Commander complex, which function as the body's "postal workers." The new understanding opens the door to new drugs and modalities for fighting everything from Alzheimer's to infectious diseases to cancer.

Found throughout the human body, the 16-strong protein group called the Commander complex is involved with myriad biological functions including mounting our immune response, maintaining homeostasis in cells, and working as sort of a delivery and routing system.

“Just as the postal system has processes to transport and sort cargo, cells in our bodies have molecular machines that transport and sort proteins,” said Prof. Brett Collins from the University of Queensland in Australia. “Cargo transport is all about getting the right parcels to the right destination at the right time and in cells, the Commander complex controls this system to ensure the right amount of protein is delivered to the right place.”

The complex has also been linked to multiple diseases includ
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Scientists use AI to identify likely drug targets in search for Alzheimer's cure
https://medicalxpress.com/news/2023-05- ... eimer.html
by Anna C. Christensen, University of Arizona
Researchers at the University of Arizona College of Medicine–Tucson, along with collaborators at Harvard University, harnessed the power of artificial intelligence to identify causes of Alzheimer's disease and potential drug targets by looking deep into the human brain to map the molecular changes that healthy neurons undergo as the disease progresses. The results are published in Communications Biology.

One of medicine's most perplexing problems is Alzheimer's disease, a neurodegenerative disorder that causes dementia, memory loss, personality changes and other irreversible symptoms. Drugs can treat symptoms of the disease, but finding a cure has been challenging, possibly because the cause of Alzheimer's disease is unclear.

"There are multiple pathways involved in Alzheimer's disease," Rui Chang, associate professor of neurology, said of the sequence of events that occur in cells to trigger changes in the body. "This is the first study showing that the AI and big data-driven approach could open the door to develop treatment for Alzheimer's by targeting new pathways or combinations of pathways."

With tissue samples from more than 2,000 Alzheimer's brains taken from a national database, Chang's AI algorithm drew from a deep well of information about genetic and molecular processes, returning a computational network model of the human brain. His team can now see maps of whole-genome genes that work together and can track the sequential changes in these genes' relationships as Alzheimer's develops, providing clues to the disease's origins and tracing the molecular path from health to disease.
Rui Chang, an associate professor of neurology, is leading a team at t
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Researchers identify 10 pesticides toxic to neurons involved in Parkinson's
https://medicalxpress.com/news/2023-05- ... inson.html
by University of California, Los Angeles
Researchers at UCLA Health and Harvard have identified 10 pesticides that significantly damaged neurons implicated in the development of Parkinson's disease, providing new clues about environmental toxins' role in the disease.

While environmental factors such as pesticide exposure have long been linked to Parkinson's, it has been harder to pinpoint which pesticides may raise risk for the neurodegenerative disorder. Just in California, the nation's largest agricultural producer and exporter, there are nearly 14,000 pesticide products with over 1,000 active ingredients registered for use.

Through a novel pairing of epidemiology and toxicity screening that leveraged California's extensive pesticide use database, UCLA and Harvard researchers were able to identify 10 pesticides that were directly toxic to dopaminergic neurons. The neurons play a key role in voluntary movement, and the death of these neurons is a hallmark of Parkinson's.

Further, the researchers found that co-exposure of pesticides that are typically used in combinations in cotton farming were more toxic than any single pesticide in that group.
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40 Hz vibrations reduce Alzheimer's pathology, symptoms in mouse models
https://medicalxpress.com/news/2023-05- ... ptoms.html
by Massachusetts Institute of Technology

Evidence that non-invasive sensory stimulation of 40 Hz gamma frequency brain rhythms can reduce Alzheimer's disease pathology and symptoms, already shown with light and sound by multiple research groups in mice and humans, now extends to tactile stimulation. A new study by MIT scientists shows that Alzheimer's model mice exposed to 40 Hz vibration an hour a day for several weeks showed improved brain health and motor function compared to untreated controls.

The MIT group is not the first to show that gamma frequency tactile stimulation can affect brain activity and improve motor function, but they are the first to show that the stimulation can also reduce levels of the hallmark Alzheimer's protein phosphorylated tau, keep neurons from dying or losing their synapse circuit connections, and reduce neural DNA damage.

"This work demonstrates a third sensory modality that we can use to increase gamma power in the brain," said Li-Huei Tsai, corresponding author of the study, director of The Picower Institute for Learning and Memory and the Aging Brain Initiative at MIT, and Picower Professor in the Department of Brain and Cognitive Sciences (BCS).
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Researchers find new potential drug target for Alzheimer's disease
https://medicalxpress.com/news/2023-05- ... sease.html
by Katie Malatino, Rensselaer Polytechnic Institute
Chunyu Wang, Ph.D., professor of biological sciences at Rensselaer Polytechnic Institute, has added to his body of research on Alzheimer's disease with significant findings now published in Angewandte Chemie.

Together with his team, which includes first author and Rensselaer doctoral student Dylan Mah, Wang performed the most comprehensive study to date of the interactions between ApoE, or Apolipoprotein E, and heparan sulfate (HS). ApoE is a protein that combines with fats to transport cholesterol throughout the body. Heparan sulfate is a sugar molecule present on cell surfaces that plays a key role in cellular communication. A variant of ApoE, ApoE4, is the most significant genetic risk for late-onset Alzheimer's disease.

"It's tremendously interesting to explore why ApoE4 can increase Alzheimer's risk," said Wang.

Wang's team investigated not only ApoE4, but ApoE3, the most common ApoE genotype and two protective isoform ApoE2 and ApoE Christchurch, as well. They discovered that the 3-O-sulfo (3-O-S) modification of HS was important for ApoE/HS interactions. All isoforms of ApoE recognized 3-O-S, but the differences in their strength of interactions correlated with Alzheimer's disease risk.

"In the initial glycan array experiment, which is basically a chip with a collection of different heparan sulfate oligosaccharide on it, we flowed ApoE over it," said Mah. "We were quite surprised to see that it had a binding pattern that looked very similar to Tau protein. It binds very well to the 3-O sulfated structures."

Tau protein is implicated in many neurogenerative diseases, including Alzheimer's.

The team's findings point to a new potential drug target to slow the progress of the disease: the enzymes responsible for sulfation called heparan sulfate 3-O transferases.
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Poorly insulated nerve cells shown to promote Alzheimer's disease in old age
https://medicalxpress.com/news/2023-06- ... shown.html
by Max Planck Society
Alzheimer's disease, an irreversible form of dementia, is considered the world's most common neurodegenerative disease. The prime risk factor for Alzheimer's is age, although it remains unclear why. It is known that the insulating layer around nerve cells in the brain, named myelin, degenerates with age. Researchers at the Max Planck Institute (MPI) for Multidisciplinary Sciences in Göttingen have now shown that such defective myelin actively promotes disease-related changes in Alzheimer's. Slowing down age-related myelin damage could open up new ways to prevent the disease or delay its progression in the future.

What was I about to do? Where did I put the keys? When was that appointment again? It starts with slight memory lapses, followed by increasing problems to orient, to follow conversations, to articulate, or to perform simple tasks. In the final phase, patients are most often care-dependent. Alzheimer's disease progresses gradually and mainly affects the elderly. The risk of developing Alzheimer's doubles every five years after the age of 65.
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