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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Class of diabetes drugs cuts dementia risk in older adults, research shows
https://medicalxpress.com/news/2022-12- ... older.html
by Erin Howe, University of Toronto

A class of medication for type 2 diabetes may help older people with the condition reduce their risk of dementia.

The findings are contained in a new study by Walter Swardfager, an assistant professor of pharmacology and toxicology at the Temerty Faculty of Medicine and a scientist in the Sandra Black Centre for Brain Resilience and Recovery at Sunnybrook Research Institute, and graduate student Che-Yuan (Joey) Wu. Their research is published in the journal Diabetes Care.

The research shows that sodium-glucose cotransporter-2 (SGLT2) inhibitors are associated with a 20% lower dementia risk when compared to another kind of medication known as dipeptidyl peptidase-4 inhibitors (DPP4).

Often, the first medication prescribed to people with type 2 diabetes is metformin. When metformin alone doesn't have the desired effect, additional therapies such as SGLT2 and DPP4 inhibitors may be added or substituted. For many patients, physicians will choose between these two classes of drugs.

SGLT2 inhibitor medications, which include dapagliflozin and empagliflozin, are commonly prescribed. These drugs lower blood sugar by causing the kidneys to remove sugar from the body through urine. DPP4 inhibitor medications—which include linagliptin, saxagliptin and sitagliptin—work by blocking the action of an enzyme that destroys an insulin-producing hormone.

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New evidence links nasal viral infections to rapid Alzheimer's progression
By Rich Haridy
December 18, 2022
https://newatlas.com/science/nasal-vira ... s-disease/

A new study has presented more evidence backing up a hypothesis suggesting viral infections in the olfactory system can accelerate the progression of Alzheimer's disease (AD). Instead of focusing on specific viruses, the research looked at the relationship between biomarkers of viral infections and neurodegeneration in the hippocampus.

For decades, researchers have reported an association between brain diseases and acute viral infections. The herpes simplex virus in particular has long been associated with the development of Alzheimer's disease. But exactly how viral infections could be influencing neurodegeneration has been unclear.

This new research focused specifically on the olfactory system. Loss of one's sense of smell has been found to be a potential early marker of Alzheimer's neurodegeneration. So, the question explored here is whether viral infections in the nose play a role in accelerating Alzheimer's decline.

To investigate this, the researchers analyzed post-mortem brain tissue from several individuals who died with Alzheimer's disease. Compared to tissue samples taken from age-matched cognitively healthy subjects, the Alzheimer's group displayed substantial markers of viral infection and inflammation in the olfactory tract – a key pathway that leads to the hippocampus.

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Researchers develop blood test that can reliably detect Alzheimer’s disease
https://www.engadget.com/researchers-de ... 20271.html

When doctors need to confirm an Alzheimer's diagnosis, they often turn to a combination of brain imaging and cell analysis. Both have their downsides. The latter involves a lumbar puncture, an invasive and painful procedure that’s more commonly known as a spinal tap. A doctor will insert a needle into the lower back to extract a sample of the patient’s cerebrospinal fluid. A lab technician then tests the sample for signs of progressive nerve cell loss and excessive amyloid and tau protein accumulation. MRI scans are less invasive but they’re often expensive and accessibility is an issue; not every community has access to the technology.

The next best tool for diagnosing Alzheimer’s disease is a blood test. While some can detect abnormal tau protein counts, they’re less effective at spotting the telltale signs of neurodegeneration. But that could soon change. This week, in the journal Brain, a multinational team made up of researchers from Sweden, Italy, the UK and US detailed a new antibody-based blood test they recently developed. The new test can detect brain-derived tau proteins, which are specific to Alzheimer’s disease. Following a study of 600 patients, the team found their test could reliably distinguish the illness from other neurodegenerative diseases.

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FDA approves new Alzheimer's drug that appears to slow progression of disease
Source: NBC News

The Food and Drug Administration on Friday approved an Alzheimer’s drug shown in clinical trials to slow cognitive decline in patients in the early stages of the illness. The approval offers patients renewed hope after repeated failures to find effective treatments, even though there have been reports of side effects with the new drug, experts say.

The drug, lecanemab, which will be sold under the name Leqembi, is a monoclonal antibody infusion given every two weeks. The FDA approved Leqembi for use in people with mild cognitive impairment or early Alzheimer’s disease. The drug was approved in an accelerated pathway, which allows early approval for promising new medications that "fill an unmet medical need."

At the same time, companies are required to conduct additional clinical trials to confirm the benefits of their drugs or risk their removal from the market. The agency said its decision was based on a phase 3 clinical trial of 1,795 patients, which found the drug, developed by drugmakers Eisai and Biogen, slowed cognitive decline in people who received it by 27% after 18 months.

The FDA did not seek the advice of its advisory committee — which it did do before it controversially approved another Alzheimer’s drug developed by Biogen, called Aduhelm, in 2021. Leqembi is not a cure; it aims to slow the progression of the disease by removing clumps of beta-amyloid — long thought by scientists to be one of the main causes of the disease — from the brain.

Read more: https://www.nbcnews.com/health/health-n ... -rcna62928

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Human-approved medication brings back 'lost' memories in mice
https://medicalxpress.com/news/2023-01- ... -mice.html
by University of Groningen

Students sometimes pull an all-nighter to prepare for an exam. However, research has shown that sleep deprivation is bad for your memory. Now, University of Groningen neuroscientist Robbert Havekes discovered that what you learn while being sleep deprived is not necessarily lost, it is just difficult to recall.

Together with his team, he has found a way to make this "hidden knowledge" accessible again days after studying while sleep-deprived using optogenetic approaches, and the human-approved asthma drug roflumilast. These findings were published in the journal Current Biology.

Havekes, associate professor of Neuroscience of Memory and Sleep at the University of Groningen, the Netherlands, and his team have extensively studied how sleep deprivation affects memory processes. "We previously focused on finding ways to support memory processes during a sleep deprivation episode," says Havekes. However, in his latest study, his team examined whether amnesia as a result of sleep deprivation was a direct result of information loss, or merely caused by difficulties retrieving information.

"Sleep deprivation undermines memory processes, but every student knows that an answer that eluded them during the exam might pop up hours afterwards. In that case, the information was, in fact, stored in the brain, but just difficult to retrieve."

Neurons in the hippocampus

To address this question, Havekes and his team used an optogenetic approach: using genetic techniques, they caused a light-sensitive protein (channelrhodopsin) to be produced selectively in neurons that are activated during a learning experience. This made it possible to recall a specific experience by shining light on these cells. "In our sleep deprivation studies, we applied this approach to neurons in the hippocampus, the area in the brain where spatial information and factual knowledge are stored," says Havekes.

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New test could detect Alzheimer's disease 3.5 years before clinical diagnosis
https://medicalxpress.com/news/2023-01- ... nosis.html
by King's College London

New research from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King's College London has established a blood-based test that could be used to predict the risk of Alzheimer's disease up to 3.5 years before clinical diagnosis.

The study, published in the journal Brain, supports the idea that components in the human blood can modulate the formation of new brain cells, a process termed neurogenesis. Neurogenesis occurs in an important part of the brain called the hippocampus that is involved in learning and memory.

While Alzheimer's disease affects the formation of new brain cells in the hippocampus during the early stages of the disease, previous studies have only been able to study neurogenesis in its later stages through autopsies.

To understand the early changes, researchers collected blood samples over several years from 56 individuals with Mild Cognitive Impairment (MCI), a condition where someone will begin to experience a worsening of their memory or cognitive ability. While not everyone experiencing MCI goes on to develop Alzheimer's disease, those with the condition progress to a diagnosis at a much higher rate than the wider population. Of the 56 participants in the study, 36 went on to receive a diagnosis of Alzheimer's disease.

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Potential therapeutic target for schizophrenia identified

by Melissa Rohman, Northwestern University
https://medicalxpress.com/news/2023-02- ... renia.html

Targeting calcium signaling in neurons represents a promising therapeutic approach for treating a rare form of schizophrenia, according to a Northwestern Medicine study published in Biological Psychiatry.

"This is the first time that human neurons are made and characterized from schizophrenia patients with the 16p11.2 duplication, one of the most prominent genetic risk factors in schizophrenia, and the first time that calcium signaling is found as a central abnormality in schizophrenia neurons," said Peter Penzes, Ph.D., the Ruth and Evelyn Dunbar Professor of Psychiatry and Behavioral Sciences and senior author of the study.

Schizophrenia is characterized by auditory and visual hallucinations, delusions, and trouble with forming and sorting thoughts, which severely impacts productivity and overall quality of life. The disease, which affects roughly one percent of the general population, has strong genetic associations, however the exact genes involved are unknown.

Patients with schizophrenia can be treated with antipsychotics, however those drugs only address "positive symptoms," such as hallucinations and delusions, and neglect to treat cognitive symptoms such as thought disorder. Despite the availability of antipsychotics, only some patients will respond to them and the development of new treatments has been met with challenges, according to Penzes.

"This has been hampered by the fact that studies in animal models, such as mice, do not translate well to humans. In other words, some new drugs may work well in experimental animal studies, but fail when taken into human clinical trials," said Penzes, who is also a professor of Neuroscience, of Pharmacology and director of the Center for Autism and Neurodevelopment.

A potential solution to developing new therapies for schizophrenia is induced pluripotent stem cells (iPSCs), cells derived from a patient's blood or skin that can be reprogrammed to be any type of cell in the body, including neurons.

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Study Suggests Fructose Could Drive Alzheimer’s Disease
February 13 , 2023

Introduction:

(EurekAlert) AURORA, Colo. (Feb. 13, 2023) – An ancient human foraging instinct, fueled by fructose production in the brain, may hold clues to the development and possible treatment of Alzheimer’s disease (AD), according to researchers at the University of Colorado Anschutz Medical Campus.

The study, published recently in The American Journal of Clinical Nutrition, offers a new way of looking at a fatal disease characterized by abnormal accumulations of proteins in the brain that slowly erode memory and cognition.

“We make the case that Alzheimer’s disease is driven by diet,” said the study’s lead author Richard Johnson, MD, professor at the University of Colorado School of Medicine specializing in renal disease and hypertension. The study co-authors include Maria Nagel, MD, research professor of neurology at the CU School of Medicine.

Johnson and his team suggest that AD is a harmful adaptation of an evolutionary survival pathway used in animals and our distant ancestors during times of scarcity.

Conclusion:

We suggest that both dietary and pharmacologic trials to reduce fructose exposure or block fructose metabolism should be performed to determine if there is potential benefit in the prevention, management or treatment of this disease,” Johnson said.

Read more here: https://www.eurekalert.org/news-releases/979532

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Children's bad dreams linked to a higher risk of dementia and Parkinson's disease in adulthood, finds new study

by Abidemi Otaiku, The Conversation
https://medicalxpress.com/news/2023-02- ... entia.html

Can children's dreams foretell events that will happen nearly 40 years into the future? Yes, according to the results of my latest study published in the journal eClinicalMedicine.

More specifically, it showed that children who experience regular bad dreams and nightmares between the ages of seven and 11, may be nearly twice as likely to develop cognitive impairment (the core feature of dementia) by the time they reach age 50. And they may be up to seven times more likely to be diagnosed with Parkinson's disease by age 50.

For some background to these startling findings, in 2022 I discovered that middle-aged and older adults who experience frequent bad dreams and nightmares could be more than twice as likely to develop dementia or Parkinson's in the future.

Given that a large proportion of people who experience regular nightmares as adults also report having had regular nightmares when they were children, this made me wonder whether having lots of bad dreams during childhood might predict the development of dementia or Parkinson's disease later in life.

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Alzheimer's: New study supports amyloid hypothesis but suggests alternative treatment
https://medicalxpress.com/news/2023-03- ... tment.html
by Columbia University

An analysis of human brain cells provides new evidence in support of the "amyloid hypothesis," the prevailing idea that Alzheimer's is caused by the accumulation of beta-amyloid proteins in the brain.

In the study, Columbia University researchers found that amyloid sparks an alliance between two proteins in the brain's neurons and this pairing is linked to about half of the gene changes that are known to occur in the disease, triggering the rapid accumulation of tau proteins, a primary driver of neurodegeneration in the disease.

"This protein pair seems very central to the disease, and because it does not appear to have another function in the brain, it is a good target for a new therapy," says the study's senior author, Ulrich Hengst, Ph.D., associate professor of pathology & cell biology (in the Taub Institute for Research on Alzheimer's Disease and the Aging Brain) at the Columbia University Vagelos College of Physicians and Surgeons.