Evaluation of CSF and plasma tau species as fluid surrogate candidates for tau PET in prodromal to moderate Alzheimer's disease

INTRODUCTION Positron emission tomography (PET) is a valuable tool for assessing tau pathology in Alzheimer's disease (AD), but it is not widely accessible. Clarifying the relationship between fluid tau species and tau PET in AD may allow for the identification of fluid biomarkers that could serve as more accessible surrogates for tau PET. METHODS Cerebrospinal fluid (CSF) and plasma tau species levels were assessed across prodromal to moderate AD subjects (CSF: n = 53, plasma: n = 181) via immunoassays and liquid chromatography‐mass spectrometry. Fluid measures were correlated with [ 18 F]GTP1 tau PET at baseline for head‐to‐head comparisons across analytes. RESULTS CSF C2N‐eMTBR‐tau243, tau phosphorylated at threonine 205 (p‐tau205), p‐tau217, and a peptide from the tau‐441 microtubule‐binding region (MTBR) (MTBR/243‐254) exhibited the highest correlations with [ 18 F]GTP1 standardized uptake value ratio. Plasma p‐tau181 and p‐tau217 demonstrated correlation rankings with tau PET similar to those observed with corresponding CSF analytes. DISCUSSION CSF C2N‐eMTBR‐tau243, MTBR/243‐254, p‐tau205, and p‐tau217 demonstrated comparable strong correlations with tau PET. These findings may guide future development of plasma biomarker surrogates for tau PET.