Specific associations between plasma biomarkers and postmortem amyloid plaque and tau tangle loads

Several promising plasma biomarkers for Alzheimer's disease have been recently developed, but their neuropathological correlates have not yet been fully determined. To investigate and compare independent associations between multiple plasma biomarkers (p-tau181, p-tau217, p-tau231, A beta 42/40, GFAP, and NfL) and neuropathologic measures of amyloid and tau, we included 105 participants from the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND) with antemortem plasma samples and a postmortem neuropathological exam, 48 of whom had longitudinal p-tau217 and p-tau181. When simultaneously including plaque and tangle loads, the A beta 42/40 ratio and p-tau231 were only associated with plaques (rho(A beta 42/40)[95%CI] = -0.53[-0.65, -0.35], rho(p-tau231)[95%CI] = 0.28[0.10, 0.43]), GFAP was only associated with tangles (rho(GFAP)[95%CI] = 0.39[0.17, 0.57]), and p-tau217 and p-tau181 were associated with both plaques (rho(p-tau217)[95%CI] = 0.40[0.21, 0.56], rho(p-tau181)[95%CI] = 0.36[0.15, 0.50]) and tangles (rho(p-tau217)[95%CI] = 0.52[0.34, 0.66]; rho(p-tau181)[95%CI] = 0.36[0.17, 0.52]). A model combining p-tau217 and the A beta 42/40 ratio showed the highest accuracy for predicting the presence of Alzheimer's disease neuropathological change (ADNC, AUC[95%CI] = 0.89[0.82, 0.96]) and plaque load (R-2 = 0.55), while p-tau217 alone was optimal for predicting tangle load (R-2 = 0.45). Our results suggest that high-performing assays of plasma p-tau217 and A beta 42/40 might be an optimal combination to assess Alzheimer's-related pathology in vivo.

Automated summary

Several promising plasma biomarkers for Alzheimer's disease have been developed, but their neuropathological correlates are not fully understood. This study investigates the associations between multiple plasma biomarkers and amyloid and tau neuropathological measures. The results suggest that plasma p-tau217 and A beta 42/40 might be an optimal combination for assessing Alzheimer's-related pathology.