Plasma p-tau217 and GFAP correlate with quantitative postmortem Alzheimer's pathology

An observational analysis in Alzheimer's & Dementia examined associations between blood-based biomarkers and quantitative postmortem neuropathology in 124 participants from the Massachusetts Alzheimer's Disease Research Center Longitudinal Cohort Study. Researchers measured plasma p-tau217, p-tau181, total tau, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) using the Meso Scale Discovery platform. Postmortem measures included amyloid-beta plaques, AT8-positive phosphorylated-tau neurons, cortical thickness, and GFAP-positive astrocytes across temporal, frontal, and occipital lobes.

Plasma p-tau217 was strongly associated with amyloid plaques, particularly neuritic plaques, and AT8-positive neurons. Associations were weaker for p-tau181 and total tau. NfL was associated only with lower cortical thickness. Plasma GFAP correlated with amyloid plaques, AT8-positive neurons, and cortical and white matter GFAP-positive astrocytes. Mediation analyses implicated p-tau217 and GFAP in the association between amyloid plaques and AT8-positive neurons.

The findings support the biological specificity of these biomarkers for distinct neuropathologic processes, extending validation beyond PET comparisons. However, observational associations and mediation analyses do not establish causality or clinical diagnostic performance. The available abstract provides no effect sizes, diagnostic accuracy estimates, or timing between blood sampling and death; full text was unavailable for assessment.