Moscoso, A;
Karikari, TK;
Grothe, MJ;
Ashton, NJ;
Lantero-Rodriguez, J;
Snellman, A;
Zetterberg, H;
... Schöll, M; + view all
(2022)
CSF biomarkers and plasma p-tau181 as predictors of longitudinal tau accumulation: Implications for clinical trial design.
Alzheimer's and Dementia
10.1002/alz.12570.
(In press).
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Abstract
Introduction: 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.
| Type: | Article |
|---|---|
| Title: | CSF biomarkers and plasma p-tau181 as predictors of longitudinal tau accumulation: Implications for clinical trial design |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/alz.12570 |
| Publisher version: | https://doi.org/10.1002/alz.12570 |
| Language: | English |
| Additional information: | © 2022 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10144765 |
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