Brain Aß load association and sexual dimorphism of plasma BACE1 concentrations in cognitively normal individuals at risk for AD.
Alzheimers Dement
; 15(10): 1274-1285, 2019 10.
Article
em En
| MEDLINE
| ID: mdl-31627825
ABSTRACT
INTRODUCTION:
Successful development of effective ß-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 ε4) 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-ß (Aß) 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 Aß-positron emission tomography global standard uptake value ratios.DISCUSSION:
Our results suggest a sexual dimorphism in BACE1-related upstream mechanisms of brain Aß 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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeos beta-Amiloides
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Ácido Aspártico Endopeptidases
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Secretases da Proteína Precursora do Amiloide
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Doença de Alzheimer
Tipo de estudo:
Etiology_studies
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Qualitative_research
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Risk_factors_studies
Limite:
Aged
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article