Yakoub, Yara;
Ashton, Nicholas J;
Strikwerda-Brown, Cherie;
Montoliu-Gaya, Laia;
Karikari, Thomas K;
Kac, Przemysław R;
Gonzalez-Ortiz, Fernando;
... PREVENT-AD Research Group; + view all
(2023)
Longitudinal blood biomarker trajectories in preclinical Alzheimer's disease.
Alzheimer's & Dementia
10.1002/alz.13318.
(In press).
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Abstract
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.
| Type: | Article |
|---|---|
| Title: | Longitudinal blood biomarker trajectories in preclinical Alzheimer's disease |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/alz.13318 |
| Publisher version: | https://doi.org/10.1002/alz.13318 |
| Language: | English |
| Additional information: | © 2023 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 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
| Keywords: | Alzheimer's disease, Aβ, PET, biomarker, pTau, plasma |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences 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 UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10172047 |
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