Blood-platelet screening in midlife could identify early risk for Alzheimer’s disease

(Press-News.org) SAN ANTONIO, Nov. 10, 2025 – A simple blood test for platelet activity at middle age could one day help identify people at risk for Alzheimer’s disease decades ahead of time, allowing for possible preventive therapy.

The blood-clotting process in vascular dysfunction is linked to key markers of Alzheimer’s as early as midlife, a study co-led by researchers at The Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases at UT Health San Antonio, the academic health center of The University of Texas at San Antonio, and the New York University Grossman School of Medicine shows.

Vascular dysfunction refers to a condition in which blood vessels do not function properly, with a number of causes from abnormal blood clots to atherosclerosis, inflammation, diabetes, high blood pressure, smoking and age. It generally is recognized as contributing to the risk of Alzheimer’s and related dementias, but the underlying mechanisms have been unclear.

The team led by the Biggs Institute and NYU identifies one of those mechanisms – platelet aggregation, the process by which platelets or small blood cells form a clot.

Specifically, the scientists link the platelet aggregation response in the blood to positron emission tomography (PET) and magnetic resonance imaging (MRI) brain markers of Alzheimer’s disease risk in middle-aged people. The breakthrough could have broad implications for both diagnosing the disease and identifying new therapies at an early stage of aging, many years before Alzheimer’s symptoms are evident.

“We believe that since platelets are easy to obtain in the blood, they could eventually become part of midlife screening to identify people at risk and apply preventive interventions targeting platelet-related inflammation,” said Sudha Seshadri, MD, professor of neurology, founding director of the Biggs Institute and senior author of the study, “Association of Platelet Aggregation With Markers of Alzheimer Disease Pathology in Middle-Aged Participants of the Framingham Heart Study,” published Nov. 4 in the journal Neurology.

Vascular component of Alzheimer’s

A vascular component of Alzheimer’s disease has been discussed since the 1960s, but a key limitation in defining it has been its frequent overlap with cerebrovascular disease, the study notes.

Up to 75% of patients diagnosed with Alzheimer’s also show vascular pathology, and 25% of patients with vascular dementia over the age of 75 show amyloid pathology, an indicator of increased risk of Alzheimer’s.

The new study analyzed 382 dementia-free participants with an average age of 56 enrolled in the Framingham Heart Study, a long-term and ongoing community-based observational study of residents in Framingham, Massachusetts, dating to 1948.

Researchers previously had identified that among middle-aged Framingham participants free of anti-platelet therapy, platelet aggregation was independently associated with the risk of incident dementia during a 20-year follow-up, adjusting for potential demographic and clinical variables.

So scientists this time sought an association between platelet aggregation and actual Alzheimer’s biomarkers at midlife.

The Framingham study has one of the largest repositories of platelet aggregation data and Alzheimer’s biomarkers available. And PET imaging, a nuclear medicine technique that uses radioactive tracers to create detailed images of organs and tissues in the body, was acquired in conjunction with MRI from a large subsample of middle-aged participants in Framingham’s third-generation cohort.

The research team measured platelet aggregation in the Framingham participants using a leading laboratory test for diagnosing platelet dysfunction called light transmission aggregometry (LTA). Then, they evaluated associations between platelet aggregation and amyloid and tau – the hallmark proteins of Alzheimer’s – on PET and MRI brain scans.
 
The results indicated a positive link: People whose platelets clump together more strongly also tend to have higher levels of amyloid and tau proteins in the brain, which are hallmarks of Alzheimer’s disease.

However, this link isn’t the same across everyone.

“The relationship shows up in people whose platelets are at the lowest end of the activity scale with the experiments that were used,” said Alexa Beiser, professor of biostatistics at the Boston University School of Public Health who has been working with Framingham data for decades and played a fundamental role in the statistical analysis of the study. “In that group, stronger platelet clumping goes hand-in-hand with more amyloid and tau on brain scans. For people with higher platelet activity, the relationship is less clear.”,

Still, the scientists concluded that circulating platelets in the blood may offer early clues to Alzheimer’s risk – perhaps decades before symptoms appear – with the data suggesting that certain features of the platelets in midlife may be tied to early brain changes linked to the disease.

“Our study underscores the need to further clarify the role of platelet-mediated inflammation in brain aging disorders and Alzheimer’s disease and related dementias in particular,” said Jaime Ramos-Cejudo, PhD, assistant professor of psychiatry and neurology at NYU, and first author of the study. “This may open new opportunities for interventions many years before symptoms are evident. We believe platelets may represent a unique bridge between vascular dysfunction and brain inflammation.”

Ramos-Cejudo is principal investigator of a new five-year, $8 million grant award from the National Institute on Aging of the National Institutes of Health to further study how peripheral inflammation, and platelet activity in particular, contribute to brain aging and the progression of Alzheimer’s and related dementias.

Mohamad Habes, PhD, director of the neuroimaging core at the Biggs Institute, and Beiser are sub-award principal investigators for the grant.

Other authors of the just-published study additionally are with Harvard Medical School, University of California-Davis and the Hemostasis and Platelet Biology Lab at the National Heart, Lung, and Blood Institute of Framingham, Massachusetts.

The Biggs Institute soon will be housed in the new $100 million Center for Brain Health at UT Health San Antonio, set to open in December, and with a ribbon-cutting this Wednesday, Nov. 12. The 103,000-square-foot center is designed to provide a comprehensive and hopeful experience for individuals facing neurological diseases, while advancing the science behind diagnosis and treatment.

 

Association of Platelet Aggregation With Markers of Alzheimer Disease Pathology in Middle-Aged Participants of the Framingham Heart Study

Jaime Ramos-Cejudo, Alexa S. Beiser, Sophia Lu, Jeremy A. Tanner, Matthew R. Scott, Tianshe He, Saptaparni Ghosh, Keith A. Johnson, Joel Salinas, Omonigho M. Bubu, Els Fieremans, Antonio Convit, Nunzio Pomara, Thomas Wisniewski, Jeffrey Berger, Ricardo S. Osorio, Charles S. Decarli, Andrew D. Johnson, Sudha Seshadri

Published Nov. 4, 2025, in Neurology

Link to study: https://www.neurology.org/doi/10.1212/WNL.0000000000214314


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The Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases at UT Health San Antonio is dedicated to providing comprehensive dementia care while advancing treatment through clinical trials and research. The Biggs Institute is a National Institute on Aging (NIA)-designated Alzheimer’s Disease Research Center (ADRC). UT Health San Antonio is the academic health center of The University of Texas at San Antonio (UT San Antonio). In addition to providing patient care and conducting research, the Biggs Institute partners with the School of Nursing at UT San Antonio to offer the Caring for the Caregiver program. 

 

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