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; PREVENT-AD Research Group

doi:10.1002/alz.13318

Longitudinal blood biomarker trajectories in preclinical Alzheimer's disease

Alzheimers Dement. 2023 Jun 9. doi: 10.1002/alz.13318. Online ahead of print.

Authors

Yara Yakoub¹, Nicholas J Ashton^{2

3

4

5}, Cherie Strikwerda-Brown¹, Laia Montoliu-Gaya², Thomas K Karikari², Przemysław R Kac², Fernando Gonzalez-Ortiz², Jonathan Gallego-Rudolf¹, Pierre-François Meyer¹, Frédéric St-Onge¹, Michael Schöll^{2

3

6}, Jean-Paul Soucy⁷, John C S Breitner^{1

8

9}, Henrik Zetterberg^{2

6

10

11

12

13}, Kaj Blennow^{2

10}, Judes Poirier^{1

8}, Sylvia Villeneuve^{1

8}; PREVENT-AD Research Group

Affiliations

¹ Douglas Mental Health University Institute, Centre for Studies on the Prevention of Alzheimer's Disease (StoP-AD), Montreal, Quebec, Canada.
² Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
³ Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway.
⁴ King's College London, Institute of Psychiatry, Psychology & Neuroscience, Maurice Wohl Clinical Neuroscience Institute, London, UK.
⁵ NIHR Biomedical Research Centre for Mental Health & Biomedical Research Unit for Dementia at South London & Maudsley NHS Foundation, London, UK.
⁶ Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, UK.
⁷ Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
⁸ Department of Psychiatry, McGill University, Montreal, Quebec, Canada.
⁹ McGill Centre for Integrative Neuroscience, McGill University, Montreal, Quebec, Canada.
¹⁰ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
¹¹ UK Dementia Research Institute at UCL, London, UK.
¹² Hong Kong Center for Neurodegenerative Diseases, Clear Water Bay, Hong Kong, China.
¹³ UW Department of Medicine, School of Medicine and Public Health, Madison, WI, USA.

PMID: 37294682
DOI: 10.1002/alz.13318

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: Aβ_42/40 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. Aβ_42/40 and pTau231 values are already abnormal at baseline in individuals with both amyloid and tau PET burden.

Keywords: Alzheimer's disease; Aβ; PET; biomarker; pTau; plasma.