Longitudinal blood biomarker trajectories in preclinical Alzheimer's disease

Yara Yakoub, Nicholas J. Ashton, Cherie Strikwerda-Brown, Laia Montoliu-Gaya, Thomas K. Karikari, Przemysław R. Kac, Fernando Gonzalez-Ortiz, Jonathan Gallego-Rudolf, Pierre François Meyer, Frédéric St-Onge, Michael Schöll, Jean Paul Soucy, John C.S. Breitner, Henrik Zetterberg, Kaj Blennow, Judes Poirier, Sylvia Villeneuve

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)


INTRODUCTION: Plasma biomarkers are altered years prior to Alzheimer's disease (AD) clinical onset. METHODS: We measured longitudinal changes in plasma amyloid-beta (Aβ)42/40 ratio, pTau181, pTau231, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) in a cohort of older adults at risk of AD (n = 373 total, n = 229 with Aβ and tau positron emission tomography [PET] scans) considering genetic and demographic factors as possible modifiers of these markers’ progression. RESULTS: Aβ42/40 ratio concentrations decreased, while NfL and GFAP values increased over the 4-year follow-up. Apolipoprotein E (APOE) ε4 carriers showed faster increase in plasma pTau181 than non-carriers. Older individuals showed a faster increase in plasma NfL, and females showed a faster increase in plasma GFAP values. In the PET subsample, individuals both Aβ-PET and tau-PET positive showed faster plasma pTau181 and GFAP increase compared to PET-negative individuals. DISCUSSION: Plasma markers can track biological change over time, with plasma pTau181 and GFAP markers showing longitudinal change in individuals with preclinical AD. Highlights: Longitudinal increase of plasma pTau181 and glial fibrillary acidic protein (GFAP) can be measured in the preclinical phase of AD. Apolipoprotein E ε4 carriers experience faster increase in plasma pTau181 over time than non-carriers. Female sex showed accelerated increase in plasma GFAP over time compared to males. Aβ42/40 and pTau231 values are already abnormal at baseline in individuals with both amyloid and tau PET burden.

Original languageEnglish
Pages (from-to)5620-5631
Number of pages12
JournalAlzheimer's and Dementia
Issue number12
Publication statusPublished - Dec 2023
Externally publishedYes


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