Associations between plasma biomarker levels and quantitative postmortem neuropathologic measures in Alzheimer's disease and related dementias.

INTRODUCTION

Validation of Alzheimer's disease blood-based biomarkers (BBMs) has relied largely on amyloid beta (Aβ) and tau positron emission tomography (PET), with limited quantitative neuropathologic correlation studies. We examined associations between BBMs and quantitative postmortem neuropathology in 124 participants from the Massachusetts Alzheimer's Disease Research Center (MADRC) Longitudinal Cohort Study.

METHODS

Plasma phosphorylated tau 217 (p-tau217), p-tau181, total tau (t-tau), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) were measured using the Meso Scale Discovery platform and correlated with postmortem quantitative measures of Aβ plaques, AT8+ pTau neurons, cortical thickness, and GFAP+ astrocytes across the temporal, frontal, and occipital lobes.

RESULTS

Plasma p-tau217 strongly associated with Aβ plaques (especially neuritic) and AT8+ neurons. Associations were weaker for p-tau181 and t-tau. NfL associated only with lower cortical thickness. GFAP correlated with Aβ plaques, AT8+ neurons, and cortical and white matter GFAP+ astrocytes. Plasma p-tau217 and GFAP mediated the association between Aβ plaques and AT8+ neurons.

DISCUSSION: These findings support BBM biological specificity and utility for in vivo characterization of distinct neuropathologic processes.