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Title: Effects of APOE-ε4 allele load on brain morphology in a cohort of middle-aged healthy individuals with enriched genetic risk for Alzheimer's disease
Author: Cacciaglia, Raffaele
Molinuevo, José Luis
Falcón, Carles
Brugulat Serrat, Anna
Sánchez Benavides, Gonzalo
Gramunt, Nina
Esteller, Manel
Moran, Sebastian
Minguillón, Carolina
Fauria, Karine
Gispert, Juan Domingo
Keywords: Malaltia d'Alzheimer
Factors de risc en les malalties
Alzheimer's disease
Risk factors in diseases
Issue Date: 28-Mar-2018
Publisher: Elsevier Masson
Abstract: INTRODUCTION: Apolipoprotein E (APOE)-ε4 is the major genetic risk factor for Alzheimer's disease. However, the dose-dependent impact of this allele on brain morphology of healthy individuals remains unclear. METHODS: We analyzed gray matter volumes (GMvs) in a sample of 533 healthy middle-aged individuals with a substantial representation of ε4-carriers (207 heterozygotes and 65 homozygotes). RESULTS: We found APOE-ε4 additive GMv reductions in the right hippocampus, caudate, precentral gyrus, and cerebellar crus. In these regions, the APOE genotype interacted with age, with homozygotes displaying lower GMv after the fifth decade of life. APOE-ε4 was also associated to greater GMv in the right thalamus, left occipital gyrus, and right frontal cortex. DISCUSSION: Our data indicate that APOE-ε4 exerts additive effects on GMv in regions relevant for Alzheimer's disease pathophysiology already in healthy individuals. These findings elucidate the mechanisms underlying the increased Alzheimer's disease risk in ε4-carriers, suggesting a dose-dependent disease vulnerability on the brain structure level.
Note: Reproducció del document publicat a:
It is part of: Alzheimer's & Dementia, 2018, vol. 14, num. 7, p. 902-912
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ISSN: 1552-5260
Appears in Collections:Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Ciències Fisiològiques)
Articles publicats en revistes (Psicologia Clínica i Psicobiologia)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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