Brain-derived tau to measure treatment effect in Alzheimer's disease and frontotemporal dementia

Abstract

INTRODUCTION: Brain-derived tau (BD-tau) measures tau specifically from brain-derived sources and can differentiate Alzheimer's disease (AD) from other diseases. This study investigated BD-tau as a potential biomarker of treatment effect. METHODS: BD-tau and phosphorylated tau-217 (p-tau217) levels were measured after treatment with an anti-tau drug in AD and behavioral variant frontotemporal dementia (bvFTD) clinical trials, and the association with total tau (t-tau), p-tau181, and amyloid beta 42 (Aβ42) was examined. RESULTS: Cerebrospinal fluid (CSF) BD-tau decreased after treatment in the AD cohort; however, no change was seen in bvFTD or p-tau217 in either cohort. CSF t-tau and p-tau181 correlated with BD-tau in AD (r = 0.9113 and 0.7746, p < 0.0001) and bvFTD (r = 1.0 and r = 0.79, p < 0.05). CSF BD-tau did not correlate with serum or plasma BD-tau in bvFTD. DISCUSSION: CSF BD-tau shows potential as a biomarker of treatment effect in AD but not bvFTD. Further research is needed to investigate this effect in blood-based samples and in other neurodegenerative diseases. Trial registration: ACTRN12611001200976, ACTRN12617001218381. Highlights: Cerebrospinal fluid (CSF) brain-derived tau (BD-tau) levels decreased with sodium selenate treatment in patients with Alzheimer's disease (AD). CSF BD-tau levels did not change with sodium selenate treatment in bvFTD. Baseline CSF BD-tau correlated with CSF total tau (t-tau) and phosphorylated tau-181 (p-tau181) in AD and behavioral variant frontotemporal dementia (bvFTD). Baseline serum and plasma BD-tau levels did not correlate with CSF BD-tau in bvFTD. CSF p-tau217 did not change with sodium selenate treatment in AD or bvFTD.