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Published on: June 14, 2020
Basic Science and Pathogenesis
Tovia Jacobs1, Jaime Ramos Cejudo1, Mark He2
1NYU Grossman School of Medicine, New York, NY, USA.
Insights
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.
Background:
Cardiovascular risk factors are among the most significant contributors to dementia, yet the biological mediators involved in this relationship need to be clarified. Prior research shows that elevated platelet aggregation is associated with an increased risk of dementia. However, comorbidities that influence platelet activity and serve as risk factors for Alzheimer's disease (AD) and related dementias (AD/ADRD) complicate this association, particularly in individuals with high vascular burden who do not have dementia. To address this, we leveraged the NIH-funded Platelet Activity and Cardiovascular Events (PACE) in patients with peripheral artery disease (PAD) and examined the relationship between platelet aggregation and AD biomarkers.
Method:
We assessed associations between platelet aggregation measured by light transmission aggregometry (LTA) and concentrations of phosphorylated tau (p-tau181), total tau, neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) in serum samples using SIMOA (Quanterix). Quantile regression models, using median cutoffs (τ=0.5), were employed to evaluate the relationships across three levels of adjustment: (1) univariate, (2) LASSO-selected covariates, and (3) adjusted by age, sex, race, and the use of platelet modifying treatments (PMT), such as aspirin or clopidogrel.
Result:
Of the 125 participants included in the analysis, 101 had complete measures of LTA exposures and all AD sera biomarkers. The median age of participants was 70 [Q1=64, Q3=77], 69.3% were male, 63.4% had poly-vascular disease (PVD), and 87.1% were on PMT (Table 1). Elevated platelet aggregation in response to submaximal doses of ADP and Epinephrine (Epi) associated with increased p-tau181 (Table 2) and NfL levels (Table 3). Associations between platelet aggregation and tau and GFAP were not observed.
Conclusion:
Although limited in sample size, our study identified associations of platelet aggregation with markers of AD pathology (p-tau181) and neurodegeneration (NfL) in PAD patients without dementia. Future studies in a larger cohort are needed to further investigate this relationship and the potential role of platelet aggregation as a mediator of AD pathology and neuroinflammatio.
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