Plasma eMTBR‐tau243 as a disease biomarker across Alzheimer's disease clinical phenotypes

INTRODUCTION: The concentration of endogenous tau microtubule-binding region containing residue-243 in plasma (eMTBR-tau243) has been proposed to be a sensitive biomarker of tangle pathology in Alzheimer's disease (AD). We assessed eMTBR-tau243 and phosphorylated tau217 (p-tau217) with tau and Aβ-positron emission tomography (PET) across different AD clinical phenotypes. METHODS: Plasma eMTBR-tau243, p-tau217, and the ratio of non-phosphorylated to phosphorylated tau217 (%p-tau217) were measured in 20 Aβ-PET positive AD patients representing four clinical phenotypes and 10 cognitively unimpaired controls. Plasma levels were correlated with PET, demographic and cognitive variables. RESULTS: Plasma eMTBR-tau243, p-tau217, and %p-tau217 levels were greater in AD than controls, with greatest levels observed in motor-predominant AD. Plasma biomarker levels correlated with cortical flortaucipir-PET uptake; eMTBR-tau243 correlations were strongest. In AD, eMTBR-tau243 levels were undetectable in patients with mild/focal flortaucipir-PET uptake (45%). Only eMTBR-tau243 correlated with cognition. DISCUSSION: Plasma eMTBR-tau243 may be an excellent biomarker for tau deposition and cognition in AD across different phenotypes.