Chemists determine the structure of the fuzzy coat that surrounds Tau proteins

MIT chemists showed they can use nuclear magnetic resonance (NMR) to decipher the structure of the fuzzy coat that surrounds Tau proteins. The findings may aid efforts to develop drugs that interfere with Tau buildup in the brain.
Image Credit: Jose-Luis Olivares, MIT; figure courtesy of the researchers
(CC BY-NC-ND 4.0)

Scientific Frontline: "At a Glance" Summary

• Discovery: MIT chemists successfully determined the atomic-level structure of the intrinsically disordered "fuzzy coat" surrounding Tau protein fibrils, a region comprising approximately 80% of the protein that was previously uncharacterizable by standard imaging.
• Methodology: The team developed a novel nuclear magnetic resonance (NMR) technique to magnetize protons within the rigid protein core and measure the transfer time to mobile segments, allowing them to map the proximity and dynamic movement of the disordered layers.
• Structural Detail: The analysis revealed a "burrito-like" architecture where the fuzzy coat wraps in layers around a rigid beta-sheet inner core, rather than extending randomly into the surrounding environment.
• Mechanism: The coat exhibits three distinct zones of mobility: a rigid core, an intermediate layer, and a highly dynamic outer layer rich in positively charged proline residues that are electrostatically repelled by the positively charged core.
• Significance: This structural model suggests that normal Tau proteins likely accumulate at the ends of existing filaments to drive fibril growth, rather than piling onto the sides, offering a precise mechanism for how Alzheimer's tangles propagate.
• Implication: Future therapeutic strategies must account for this protective layering, as small-molecule drugs intended to disaggregate Tau fibrils will need to effectively penetrate the dense fuzzy coat to reach and disrupt the toxic core.

One in four older Americans with dementia prescribed risky brain-altering drugs despite safety warnings

Photo Credit: Wikimedia Commons

Scientific Frontline: "At a Glance" Summary

• Main Discovery: One in four Medicare beneficiaries with dementia is prescribed central nervous system (CNS)-active medications—such as sedatives and antipsychotics—despite clinical guidelines warning against their use due to risks of falls, confusion, and hospitalization.
• Methodology: Researchers analyzed survey data from the Health and Retirement Study linked to Medicare fee-for-service claims from 2013 to 2021 to trace prescribing patterns of five drug classes across adults with normal cognition, cognitive impairment, and dementia.
• Data Stratification: Prescribing prevalence was highest among the most vulnerable: 25% of patients with dementia and nearly 22% of those with cognitive impairment received these drugs, compared to 17% of older adults with normal cognition.
• Specific Trends: While overall CNS-active prescriptions decreased from 20% to 16% over the study period (driven by declines in benzodiazepines and hypnotics), antipsychotic prescriptions conversely rose from 2.6% to 3.6%.
• Clinical Validity: In 2021, over two-thirds of patients receiving these prescriptions lacked a documented clinical indication, suggesting a high volume of potentially inappropriate and harmful prescribing practices.
• Significance: These findings highlight substantial opportunities to improve safety for cognitively impaired older adults, necessitating rigorous medication reviews by physicians to taper or discontinue inappropriate treatments.

AI model predicts disease risk while you sleep

SleepFM utilizes diverse physiological data streams, highlighting the potential to improve disease forecasting and better understand health risks.
Image Credit: Scientific Frontline / AI generated (Gemini)

The first artificial intelligence model of its kind can predict more than 100 health conditions from one night’s sleep.

A poor night’s sleep portends a bleary-eyed next day, but it could also hint at diseases that will strike years down the road. A new artificial intelligence model developed by Stanford Medicine researchers and their colleagues can use physiological recordings from one night’s sleep to predict a person’s risk of developing more than 100 health conditions.

Known as SleepFM, the model was trained on nearly 600,000 hours of sleep data collected from 65,000 participants. The sleep data comes from polysomnography, a comprehensive sleep assessment that uses various sensors to record brain activity, heart activity, respiratory signals, leg movements, eye movements, and more.

International research breakthrough for remote Alzheimer’s testing

Photo Credit: Courtesy of University of Exeter

A groundbreaking international study has demonstrated that Alzheimer’s disease biomarkers can be accurately detected using simple finger-prick blood samples that can be collected at home and mailed to laboratories without refrigeration or prior processing. 

The research, led by US institute Banner Health working with the University of Exeter Medical School and supported by the National Institute for Health and Care Research (NIHR), published today in Nature Medicine. It represents the first large-scale validation of this accessible testing approach that removes geographic barriers and opens brain disease research to global populations without requiring specialized healthcare infrastructure. 

The DROP-AD project, conducted across seven European medical centers including the University of Gothenburg and University of Exeter, successfully tested 337 participants and proved that finger-prick blood collection can accurately measure key markers of Alzheimer’s pathology and brain damage. This breakthrough enables worldwide research participation by eliminating the logistical constraints that have historically limited biomarker studies to well-resourced medical facilities. 

Researchers Develop Guidelines for Diagnosing, Monitoring Canine Cognitive Decline

Chimmi (04/09/2010 - 02/23/2025)
Photo Credit: Heidi-Ann Fourkiller

An international working group of canine cognition experts has released a set of guidelines for veterinarians to use in diagnosing and monitoring canine cognitive dysfunction syndrome (CCDS), or canine dementia. The guidelines offer a standard definition of the condition as well as practical diagnostic criteria and are meant to aid both clinicians and researchers in helping senior dogs with cognitive issues.

“We are seeing CCDS diagnoses with increasing frequency, but there isn’t a standardized method for the diagnosis,” says Natasha Olby, Dr. Kady M. Gjessing and Rahna M. Davidson Distinguished Chair in Gerontology at North Carolina State University. “We wanted to propose that standardized method as a starting point that can be built upon over time.” Olby is the leader of the working group and corresponding author of the work.

Researchers create cells that help the brain keep its cool

Parvalbumin cells play a central role in keeping brain activity in equilibrium. They control nervcell signalling, reduce overactivity and make sure that the brain is working to a rhythm
Image Credit: Scientific Frontline

Researchers at Lund University in Sweden have created a method that makes it possible to transform the brain’s support cells into parvalbumin-positive cells. These cells act as the brain’s rapid-braking system and are significantly involved in schizophrenia, epilepsy, and other neurological conditions. 

Parvalbumin cells play a central role in keeping brain activity in equilibrium. They control nerve cell signaling, reduce overactivity and make sure that the brain is working to a rhythm. Researchers sometimes describe them as the cells that “make the brain sound right”. 

When these cells malfunction or decrease in number, the balance of the brain is disrupted. Previous studies suggest that damaged parvalbumin cells may contribute to disorders such as schizophrenia and epilepsy.  

Psychiatry: In-Depth Description

Scientific Frontline / stock image

Psychiatry is the branch of medicine exclusively dedicated to the diagnosis, treatment, and prevention of mental, emotional, and behavioral disorders.

Unlike psychology, which is the study of the mind and behavior, psychiatry is a medical discipline. Psychiatrists are qualified medical doctors (MD or DO) who specialize in the complex intersection of physical and mental health. The primary goal of the field is to alleviate suffering and improve well-being by managing conditions ranging from transient emotional crises to chronic, life-altering mental illnesses through a combination of pharmacological, psychotherapeutic, and psychosocial interventions.

Menopause hormone therapy does not appear to impact dementia risk

Photo Credit: Vitaly Gariev

A major review of prior research has found no evidence that menopause hormone therapy either increases or decreases dementia risk in post-menopausal women, in a new study led by University College London researchers and supported by the University of Exeter. 

The findings, commissioned by the World Health Organization (WHO) and published in The Lancet Healthy Longevity, add much-needed clarity to a hotly debated topic, and reinforce current clinical guidance that menopause hormone therapy, also called hormone replacement therapy or HRT, should be guided by perceived benefits and risks and not for dementia prevention. 

Professor Chris Fox from the University of Exeter Medical School said: “The role of menopause hormone treatment and relationship to dementia is a worry for many women. But our state-of-the-art review indicates there is no evidence that menopause hormone treatment reduces or increases the risk of dementia. When deciding whether to take menopause hormone treatment, reducing one’s risk of dementia should not be part of that decision “ 

Stroke and dementia: combating loss of function in small vessels of the brain

Professor Martin Dichgans
Photo Credit: © LMU / Stephan Höck

Researchers at LMU University Hospital have elucidated how diseases of small blood vessels in the brain develop. So-called cerebral small vessel disease (CSVD) can lead to widespread consequences such as circulatory disorders, hemorrhages, and often severe strokes, and is considered one of the main causes of dementia. The scientists' results have now been published in the journal Nature Neuroscience. 

In view of the prevalence of this serious and life-threatening condition—strokes, for example, are the leading cause of long-term disability and the second leading cause of death—it is astonishing "that medicine has so far known comparatively little about the cellular and molecular mechanisms underlying the development of cerebral small vessel disease," says LMU Professor Martin Dichgans, Chair of Translational Stroke and Dementia Research, Director of the Institute for Stroke and Dementia Research (ISD) at LMU University Hospital Munich, and future spokesperson for the SyNergy Cluster of Excellence. 

What Is: Dementia

Illustration Credit: Scientific Frontline

The End of the Passive Era

The year 2025 marks a definitive inflection point in the history of neuroscience and geriatric medicine. For decades, the field of dementia care was characterized by a certain fatalism—a paradigm of "diagnose and manage" where the clinician’s role was largely to document decline and support the family. That era has officially closed. We have entered the age of precision intervention, defined by the ability to detect neurodegenerative pathology in blood plasma decades before symptoms arise, the availability of disease-modifying immunotherapies that clear toxic proteins from the brain, and a nuanced biological understanding that has shattered the monolithic concept of "senility" into a spectrum of distinct, treatable molecular events.

Our Scientific Frontline report provides an exhaustive analysis of the dementia landscape as it stands in late 2025. It synthesizes data from the latest clinical trials, including the landmark approval of subcutaneous maintenance dosing for anti-amyloid therapies, and examines the emerging economic reality where the global cost of dementia is projected to triple by mid-century. We explore the biological underpinnings of conditions ranging from classic Alzheimer’s Disease to the newly characterized Limbic-predominant Age-related TDP-43 Encephalopathy (LATE), and we evaluate the transformative potential of 14 modifiable risk factors that could prevent nearly half of all cases.

Concordia researchers identify key marker linking coronary artery disease to cognitive decline

Zacharie Potvin-Jutras, with Claudine Gauthier:
“Our goal is to examine conditions at the onset of a heart disease, before there has been any significant impact on the brain”
Photo Credit: Courtesy of Concordia University

Individuals with coronary artery disease (CAD) — a constricting or blocking of blood vessels feeding the heart — face increased risks of strokes, cognitive impairment and dementia. However, the link between CAD and cognitive function is not fully understood. 

A new study led by Concordia researchers looks at how the disease affects the brain’s white matter, the network of nerve fibers that connects different regions of the brains and is critical to transmitting information efficiently. 

The study, published in the Journal of Neuroscience, applied a novel multivariate approach using 12 separate metrics. The researchers compared test results and MRI scans of 43 patients with CAD to those of 36 healthy individuals. All participants were over the age of 50. 

Scientists uncover how the brain falls asleep

Scientists have been able to pinpoint, for the first time, the exact moment the brain transitions into sleep, and precisely map the unfolding process in real time.
Photo Credit: Zohre Nemati

In the new study, the researchers demonstrated that the human brain falls asleep abruptly, rather than gradually, with a ‘tipping point’ marking the transition from wakefulness into sleep. They were then able to predict the momentary progression into sleep with unprecedented precision. 

The findings could be used to develop new ways to diagnose and treat sleep disorders, such as insomnia, and as a marker of brain health in the context of ageing and neurodegenerative disease, and even to improve how we monitor anesthesia during surgical procedures.  

Study reveals genetic link between childhood brain disorder and Parkinson's disease in adults

Image Credit: Dmitriy Kievskiy

Errors in a gene known to cause a serious neurodevelopmental condition in infants are also linked to the development of Parkinson’s disease in adolescence and adulthood, according to new research

The study, published in the Annals of Neurology, looked at a gene called EPG5. Errors in this gene are already known to cause Vici syndrome – a rare and severe inherited neurodevelopmental condition that presents early in life and affects multiple organ systems. Now researchers at King’s College London, University College London (UCL), the University of Cologne and the Max Planck Institute for Biology of Ageing have found that errors in the same gene are linked to changes in nerve cells that lead to more common age-related conditions like Parkinson’s disease and dementia.

Cholesterol-lowering drugs could reduce the risk of dementia

Low cholesterol can reduce the risk of dementia, a new University of Bristol-led study with more than a million participants has shown.

The research, led by Dr Liv Tybjærg Nordestgaard while at the University of Bristol and the Department of Clinical Biochemistry at Copenhagen University Hospital – Herlev and Gentofte, found that people with certain genetic variants that naturally lower cholesterol have a lower risk of developing dementia.

The study, which is based on data from over a million people in Denmark, England, and Finland, has been published in the journal Alzheimer's & Dementia: The Journal of the Alzheimer's Association. 

Some people are born with genetic variants that naturally affect the same proteins targeted by cholesterol-lowering drugs, such as statins and ezetimibe. To test the effect of cholesterol-lowering medication on the risk of dementia, the researchers used a method called Mendelian Randomization — this genetic analysis technique allowed them to mimic the effects of these drugs to investigate how they influence the risk of dementia, while minimizing the influence of confounding factors like weight, diet, and other lifestyle habits.

Brain inflammation treatment could be ally in fight against dementia

Samira Aghlara-Fotovat
Photo Credit: Jeff Fitlow/Rice University

Scientists from Rice University and Houston Methodist have developed a new way to reduce inflammation in the brain, a discovery that could help fight diseases such as Alzheimer’s and Parkinson’s.

The team created “AstroCapsules,” small hydrogel capsules that enclose human astrocytes ⎯ star-shaped brain cells that support healthy nervous system function. Inside the capsules, the cells were engineered to release interleukin-1 receptor antagonist, an anti-inflammatory protein. Tests in human brain organoids and mouse models showed the treatment lowered neuroinflammation and resisted immune rejection.

Rice bioengineer Omid Veiseh, whose lab studies how to design biomaterials that work with the immune system, is co-corresponding author on the paper published in Biomaterials.

“Encapsulating cells in a way that shields them from immune attack has been a central challenge in the field,” said Veiseh, professor of bioengineering at Rice, Cancer Prevention and Research Institute of Texas Scholar and director of the Rice Biotech Launch Pad. “In our lab, we have been working on biomaterials for many years, and this project was an opportunity to draw from that experience to address the uniquely complex immune environment of the brain. Our hope is that this work will help move cell therapies closer to becoming real treatment options for patients with neurodegenerative disease.”

Does isolated REM sleep behavior disorder predict Parkinson’s disease or dementia?

Image Credit: Gerd Altmann

An international research team led by Université de Montréal medical professor Shady Rahayel has made a major breakthrough in predicting neurodegenerative diseases. 

Thanks to two complementary UdeM studies, scientists are now able to determine, years in advance, which individuals with a particular sleep disorder will develop Parkinson’s disease or dementia with Lewy bodies (DLB). 

The studies focus on isolated REM sleep behavior disorder (iRBD)—a condition in which people yell, thrash, or act out their dreams, sometimes violently enough to injure a bed partner. 

“It’s not just restless sleep—it’s a neurological warning sign,” said Rahayel, a neuropsychologist and researcher at the Centre for Advanced Research in Sleep Medicine at Sacré-Cœur Hospital in Montreal. 

Roughly 90 per cent of people with this sleep disorder will go on to eventually develop Parkinson’s disease or DLB. Until now, however, it was impossible to know which disease would occur—or when. 

Study reveals reasons for misdiagnosis of frontotemporal dementia

Researchers have discovered patterns in the misdiagnosis of frontotemporal dementia
Photo Credit: Anna Shvets

University of Queensland researchers discovered that nearly 70 per cent of suspected frontotemporal dementia patients ultimately did not have the disease, in a study aimed at identifying factors that contribute to misdiagnosis of this notoriously difficult to diagnose disorder.

Psychiatrist Dr Joshua Flavell, working with cognitive neurologist Professor Peter Nestor at the Mater Hospital Memory and Cognitive Disorders clinic and UQ’s Queensland Brain Institute, analyzed data from 100 patients suspected of having frontotemporal dementia who had been referred by specialist physicians like neurologists, psychiatrists or geriatricians.

“Of the 100 patients, 34 were true-positive, and 66 were false-positive for frontotemporal dementia,” Dr Flavell said.

“We found that misinterpretation of brain scans, particularly nuclear imaging, led to 32 patients being incorrectly diagnosed.

Patients with delirium more likely to develop dementia

Professor Ruth Hubbard interacting with a patient.
Photo Credit: The University of Queensland

University of Queensland researchers have found older patients who experience delirium are three times more likely to develop dementia.

Professor Ruth Hubbard from UQ’s Centre for Health Services Research (CHSR) said the study also found that every episode of delirium increased the chance of developing dementia by 20 per cent.

“Delirium is an acute confusional state which particularly impacts older people and can have long term detrimental effects on patients,” Professor Hubbard said.

“Our study found that it is also strongly linked to dementia.”

The researchers analyzed a cohort of more than 110,000 patients from New South Wales hospitals over five years.

Lead author and CHSR research fellow, Dr Emily Gordon, said more than 55,000 patients who had experienced delirium were compared to patients who had not.

Risk factors for faster aging in the brain revealed in new study

Governments have been urged to act decisively before 2035 to ensure global warming can be kept below 2°C by 2100.
Photo Credit: Nöel Puebla

Researchers from the Nuffield Department of Clinical Neurosciences at the University of Oxford have used data from UK Biobank participants to reveal that diabetes, traffic-related air pollution and alcohol intake are the most harmful out of 15 modifiable risk factors for dementia.

The researchers had previously identified a ‘weak spot’ in the brain, which is a specific network of higher-order regions that not only develop later during adolescence, but also show earlier degeneration in old age. They showed that this brain network is also particularly vulnerable to schizophrenia and Alzheimer’s disease.

In this new study, published in Nature Communications, they investigated the genetic and modifiable influences on these fragile brain regions by looking at the brain scans of 40,000 UK Biobank participants aged over 45.

The researchers examined 161 risk factors for dementia, and ranked their impact on this vulnerable brain network, over and above the natural effects of age. They classified these so-called ‘modifiable’ risk factors − as they can potentially be changed throughout life to reduce the risk of dementia − into 15 broad categories: blood pressure, cholesterol, diabetes, weight, alcohol consumption, smoking, depressive mood, inflammation, pollution, hearing, sleep, socialization, diet, physical activity, and education.

Human brains are getting larger. That may be good news for dementia risk

Image Credit: Dmitriy Gutarev

A new study by researchers at UC Davis Health found human brains are getting larger. Study participants born in the 1970s had 6.6% larger brain volumes and almost 15% larger brain surface area than those born in the 1930s.

The researchers hypothesize the increased brain size may lead to an increased brain reserve, potentially reducing the overall risk of age-related dementias.

The findings were published in JAMA Neurology.

“The decade someone is born appears to impact brain size and potentially long-term brain health,” said Charles DeCarli, first author of the study. DeCarli is a distinguished professor of neurology and director of the UC Davis Alzheimer’s Disease Research Center. “Genetics plays a major role in determining brain size, but our findings indicate external influences — such as health, social, cultural and educational factors — may also play a role.”