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CSF biomarkers and plasma p‐tau181 as predictors of longitudinal tau accumulation: Implications for clinical trial design
Author(s) -
Moscoso Alexis,
Karikari Thomas K.,
Grothe Michel J.,
Ashton Nicholas J.,
LanteroRodriguez Juan,
Snellman Anniina,
Zetterberg Henrik,
Blennow Kaj,
Schöll Michael
Publication year - 2022
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.12570
Subject(s) - cerebrospinal fluid , clinical trial , biomarker , oncology , positron emission tomography , medicine , amyloid beta , alzheimer's disease neuroimaging initiative , disease , nuclear medicine , alzheimer's disease , biology , biochemistry
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. Methods We included older individuals who had serial tau‐PET scans, baseline amyloid beta (Aβ)‐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. Results 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 Aβ‐PET. Prescreening with plasma p‐tau181 reduced up to ≈50% of screening failures. Discussion Clinical trials testing tau‐targeting therapies may benefit from using fluid biomarkers to recruit individuals at risk of tau aggregation.