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

Gemma Salvadó*, Rik Ossenkoppele, Nicholas J. Ashton, Thomas G. Beach, Geidy E. Serrano, Eric M. Reiman, Henrik Zetterberg, Niklas Mattsson-Carlgren, Shorena Janelidze, Kaj Blennow, Oskar Hansson*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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, Aβ42/40, 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 Aβ42/40 ratio and p-tau231 were only associated with plaques (ρAβ42/40[95%CI] = −0.53[−0.65, −0.35], ρp-tau231[95%CI] = 0.28[0.10, 0.43]), GFAP was only associated with tangles (ρGFAP[95%CI] = 0.39[0.17, 0.57]), and p-tau217 and p-tau181 were associated with both plaques (ρp-tau217[95%CI] = 0.40[0.21, 0.56], ρp-tau181[95%CI] = 0.36[0.15, 0.50]) and tangles (ρp-tau217[95%CI] = 0.52[0.34, 0.66]; ρp-tau181[95%CI] = 0.36[0.17, 0.52]). A model combining p-tau217 and the Aβ42/40 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 (R2 = 0.55), while p-tau217 alone was optimal for predicting tangle load (R2 = 0.45). Our results suggest that high-performing assays of plasma p-tau217 and Aβ42/40 might be an optimal combination to assess Alzheimer's-related pathology in vivo.
Original languageEnglish
Article numbere17123
JournalEmbo Molecular Medicine
Issue number5
Early online date2023
Publication statusPublished - 8 May 2023

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