Longitudinal Blood Biomarker Trajectories in Preclinical Alzheimer’s Disease

Background Blood-biomarkers of Alzheimer’s disease (AD) pathology have been investigated cross-sectionally in heterogenous AD cohorts and shown to detect underlying pathology, even at preclinical stages. However, longitudinal studies, including serial blood-biomarker measurements, are needed better understand whether these markers could help monitor progression. We aimed assess blood-biomarkers temporal trajectories cognitively unimpaired older adults different pathological stages as assessed by positron emission tomography (PET). This may provide insight into dynamic changes biomarkers beginning prior abnormality on PET. Method included a subset 126 from the Prevent-AD cohort. Blood was drawn baseline up four-year follow-up visits. measured Aβ42/Aβ40 ratio, pTau181 pTau231 using novel single molecular array (Simoa). All participants completed Aβ (18F-NAV4694) tau (18F-flortaucipir) PET scans, which were mostly performed latest blood collection timepoint. positivity defined global neocortical Aβ-PET retention (SUVR cut-off = 1.29), tau-PET entorhinal cortex flortaucipir binding 1.23). Using thresholds, 82 subjects classified A-T-, 29 A+T-, 15 A+T+. Linear mixed effects models used differences rate change plasma between groups. Result Amyloid-PET-positive individuals showed elevated levels pTau181, lower Aβ42/40 when compared with amyloid-PET-negative participants. Plasma greater increase over time A+T+ group A-T- (p 0.01; Figure 1). Overall, A+T- groups had 0.05, p 0.0189; 2), higher 0.0006; 3). Longitudinal did not differ Conclusion observed increased those both amyloid The slopes across despite overall level pathology.