Journal
ALZHEIMERS & DEMENTIA
Volume 15, Issue 10, Pages 1274-1285Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jalz.2019.07.001
Keywords
Plasma BACE1; Alzheimer's disease; Sexual dimorphism; BACE1 biomarkers; Disease modifying
Categories
Funding
- program PHOENIX
- Fondation pour la Recherche sur Alzheimer
- AXA Research Fund
- Fondation partenariale Sorbonne Universite
- Fondation pour la Recherche sur Alzheimer, Paris, France
- program Investissements d'avenir (Agence Nationale de la Recherche10-IA Agence Institut Hospitalo-Universitaire-6) [ANR-10-IAIHU-06]
- Agency for Innovation by Science and Technology [IWT OO 140105]
- Agency for Innovation by Science and Technology (VLAIO) [HBC.2016.0548]
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Introduction: Successful development of effective beta-site amyloid precursor protein cleaving enzyme 1 (BACE1)-targeted therapies for early stages of Alzheimer's disease requires biomarker-guided intervention strategies. Methods: We investigated whether key biological factors such as sex, apolipoprotein E (APOE epsilon 4) allele, and age affect longitudinal plasma BACE1 concentrations in a large monocenter cohort of individuals at risk for Alzheimer's disease. We explored the relationship between plasma BACE1 concentrations and levels of brain amyloid-beta (A beta) deposition, using positron emission tomography global standard uptake value ratios. Results: Baseline and longitudinal mean concentrations of plasma BACE1 were significantly higher in women than men. We also found a positive significant impact of plasma BACE1 on baseline A beta-positron emission tomography global standard uptake value ratios. Discussion: Our results suggest a sexual dimorphism in BACE1-related upstream mechanisms of brain A beta production and deposition. We argue that plasma BACE1 should be considered in further biomarker validation and qualification studies as well as in BACE1 clinical trials. (C) 2019 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer's Association.
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