To understand the interaction between plasma biomarkers of Alzheimer’s disease (AD) and cerebrovascular risk factors (CV-RF) in relation to neuropathologic change.

Plasma biomarkers for AD and neurodegeneration have shown considerable promise in early evaluation of AD and other dementias. However, chronic CV-RF can influence the interpretation of plasma biomarkers and affect the prediction results of underlying neuropathologic change.

We utilized a population-based prospective study of aging including 391 participants with autopsy and antemortem plasma biomarker assays consisting of Aβ42/40, pTau-181, GFAP, and NfL on the Simoa HD-X platform (Quanterix). CV-RF were quantified by a composite score of seven cardiovascular metabolic conditions (CMC) which includes hypertension, diabetes, heart failure, stroke, coronary artery disease, atrial fibrillation, and dyslipidemia. We predicted AD neuropathologic change (ADNC), Thal phase, Braak stage, and neuritic plaque score using a logistic regression model that allowed for interaction terms between plasma biomarkers and CMC while controlling for age and sex. 

We observed a positive interaction between ptau-181 and increasing CMC for prediction of Thal phase (High CMC OR = 4.72 vs low CMC OR = 1.08, p<0.001) and ADNC (High CMC OR = 5.26 vs low CMC OR = 1.63, p<0.001), showing greater association at high CMC. There was also a negative interaction between Aβ42/40 and CMC when predicting Braak stage (High CMC OR = 0.89 vs low CMC OR = 1.94, p<0.001), neuritic plaque score  (High CMC OR = 0.90 vs low CMC OR = 1.81, p<0.001), and ADNC (High CMC OR = 1.02 vs low CMC OR = 1.61, p<0.037), showing stronger association in those with low CMC.

Plasma biomarkers are associated with AD pathology but interact with cerebrovascular comorbidities. Vascular risk factors need to be considered in the interpretation of plasma biomarkers.