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Brain Aβ load association and sexual dimorphism of plasma BACE1 concentrations in cognitively normal individuals at risk for AD
- Source :
- ALZHEIMERS & DEMENTIA, Alzheimer's and Dementia, Alzheimer's and Dementia, Elsevier, 2019, 15, pp.1274-1285. ⟨10.1016/j.jalz.2019.07.001⟩
- Publication Year :
- 2019
- Publisher :
- ELSEVIER SCIENCE INC, 2019.
-
Abstract
- 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.
- Subjects :
- Male
0301 basic medicine
Apolipoprotein E
Epidemiology
[SDV]Life Sciences [q-bio]
PROGRESSION
Disease
Cognition
0302 clinical medicine
Amyloid precursor protein
Medicine and Health Sciences
Aspartic Acid Endopeptidases
medicine.diagnostic_test
biology
Health Policy
Settore BIO/14
Brain
Alzheimer's disease
Healthy Volunteers
3. Good health
GENOTYPE
ALZHEIMERS-DISEASE
Psychiatry and Mental health
Positron emission tomography
Cohort
Biomarker (medicine)
Female
EXPRESSION
medicine.medical_specialty
BIOMARKERS
Standardized uptake value
03 medical and health sciences
Cellular and Molecular Neuroscience
Sexual dimorphism
Apolipoproteins E
Sex Factors
Developmental Neuroscience
Alzheimer Disease
Internal medicine
mental disorders
medicine
Humans
BACE1 biomarkers
Aged
Plasma BACE1
DECLINE
Amyloid beta-Peptides
business.industry
030104 developmental biology
Endocrinology
Positron-Emission Tomography
Disease modifying
biology.protein
Neurology (clinical)
Amyloid Precursor Protein Secretases
Geriatrics and Gerontology
business
Biomarkers
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 15525260 and 15525279
- Database :
- OpenAIRE
- Journal :
- ALZHEIMERS & DEMENTIA, Alzheimer's and Dementia, Alzheimer's and Dementia, Elsevier, 2019, 15, pp.1274-1285. ⟨10.1016/j.jalz.2019.07.001⟩
- Accession number :
- edsair.doi.dedup.....5c39b752d358c0026bcce39dcced95f3