Abstract INTRODUCTION Blood‐based phosphorylated tau 217 (p‐tau217), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) show promise for Alzheimer's disease (AD), while their links to brain amyloid beta (Aβ)/tau, hippocampal atrophy, and cognitive decline need further investigation. METHODS A cohort of 1275 participants, representing various cognitive stages, was recruited to examine the links between plasma biomarkers and brain Aβ/tau stages, tau progression, hippocampal atrophy, and cognitive decline. RESULTS Plasma p‐tau217 effectively distinguished A−T−/A−T+ individuals and A+T+ Braak III–VI patients, though it identified early A+T−/A+T+ Braak I‐II stages only in Aβ+ subjects. Plasma GFAP levels plateau beyond a certain tau threshold, while Aβ‐induced tau progression occurred only in those with high GFAP. Plasma NfL showed a weak link to brain Aβ and tau pathology, hippocampal atrophy, and typical AD cognitive decline. DISCUSSION Plasma p‐tau217 aids in disease stratification, and GFAP promotes tau progression, while NfL is inadequate as a neuronal injury biomarker for AD. Highlights Plasma p‐tau217 is strongly linked to brain Aβ/tau burdens and effectively differentiates between various Aβ/tau stages. Elevated plasma levels of GFAP consistently contributed to the Aβ‐induced tau progression across various Braak stages. Plasma NfL exhibits limited associations with Aβ/tau pathology, AD‐specific hippocampal atrophy, and cognitive decline.
Pan et al. (2025) studied this question.
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