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Published on: June 14, 2020
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Basic Science and Pathogenesis.
Tovia Jacobs1, Jaime Ramos Cejudo1, Mark He2
1NYU Grossman School of Medicine, New York, NY, USA.
Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 25, 2025
Summary
Elevated platelet aggregation is linked to increased Alzheimer's disease (AD) pathology markers like p-tau181 and neurodegeneration marker NfL in peripheral artery disease (PAD) patients. Further research is needed to confirm these findings in larger cohorts.
Area of Science:
- Neurology
- Cardiovascular Medicine
- Biochemistry
Background:
- Cardiovascular risk factors significantly contribute to dementia, but underlying biological mechanisms require clarification.
- Elevated platelet aggregation is a known risk factor for dementia, complicated by comorbidities in individuals with high vascular burden.
- The Platelet Activity and Cardiovascular Events (PACE) study investigated the link between platelet activity and Alzheimer's disease (AD) biomarkers in patients with peripheral artery disease (PAD).
Purpose of the Study:
- To clarify the biological mediators linking cardiovascular risk factors to dementia.
- To examine the relationship between platelet aggregation and AD biomarkers in patients with PAD.
- To investigate potential associations between platelet activity and markers of AD pathology and neurodegeneration.
Main Methods:
- Platelet aggregation was measured using light transmission aggregometry (LTA).
- Serum concentrations of phosphorylated tau (p-tau181), total tau, neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) were quantified using SIMOA.
- Quantile regression models were used to assess associations, with adjustments for univariate, LASSO-selected covariates, and demographic/treatment factors.
Main Results:
- In 101 PAD patients, elevated platelet aggregation (with ADP and Epinephrine) correlated with increased p-tau181 and NfL levels.
- No significant associations were found between platelet aggregation and total tau or GFAP levels.
- The study cohort had a median age of 70, with a majority being male, having poly-vascular disease, and being on platelet-modifying treatments.
Conclusions:
- Platelet aggregation is associated with AD pathology (p-tau181) and neurodegeneration (NfL) markers in PAD patients without dementia.
- These findings suggest a potential role for platelet aggregation in mediating AD pathology and neuroinflammation.
- Larger cohort studies are necessary to validate these associations and explore the underlying mechanisms.
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