CSF biomarkers and plasma p-tau181 as predictors of longitudinal tau accumulation: Implications for clinical trial design

Abstract

<p><strong>Introduction</strong> Clinical trials targeting tau in Alzheimer's disease (AD) need to recruit individuals at risk of tau accumulation. Here, we studied cerebrospinal fluid (CSF) biomarkers and plasma phosphorylated tau (p-tau)181 as predictors of tau accumulation on positron emission tomography (PET) to evaluate implications for trial designs.</p><p><strong>Methods</strong> We included older individuals who had serial tau-PET scans, baseline amyloid beta (A beta)-PET, and baseline CSF biomarkers (n = 163) or plasma p-tau181 (n = 74). We studied fluid biomarker associations with tau accumulation and estimated trial sample sizes and screening failure reductions by implementing these markers into participant selection for trials.</p><p><strong>Results</strong> P-tau181 in CSF and plasma predicted tau accumulation (r > 0.36, P < .001), even in AD-continuum individuals with normal baseline tau-PET (A+T-; r > 0.37, P < .05). Recruitment based on CSF biomarkers yielded comparable sample sizes to A beta-PET. Prescreening with plasma p-tau181 reduced up to approximate to 50% of screening failures.</p><p><strong>Discussion</strong> Clinical trials testing tau-targeting therapies may benefit from using fluid biomarkers to recruit individuals at risk of tau aggregation.</p>