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Title: APOE-by-sex interactions on brain structure and metabolism in healthy elderly controls
Author: Sampedro, Frederic
Vilaplana, Eduard
De Leon, Mony J.
Alcolea, Daniel
Pegueroles, Jordi
Montal, Victor
Carmona-Iragui, María
Sala, Isabel
Sanchez-Saudinos, María Belén
Antón-Aguirre, Sofía
Morenas-Rodriguez, Estrella
Camacho, Valle
Falcon, Carles
Pavía Segura, Javier
Ros Puig, Domènec
Clarimón, Jordi
Blesa, Rafael
Lleó, Alberto
Fortea, Juan
Alzheimer's Disease Neuroimaging Initiative
Keywords: Malalties hereditàries
Malaltia d'Alzheimer
Lípids de la sang
Genetic diseases
Alzheimer's disease
Blood lipids
Issue Date: 29-Sep-2015
Publisher: Impact Journals
Abstract: BACKGROUND: The APOE effect on Alzheimer Disease (AD) risk is stronger in women than in men but its mechanisms have not been established. We assessed the APOE-by-sex interaction on core CSF biomarkers, brain metabolism and structure in healthy elderly control individuals (HC). METHODS: Cross-sectional study. HC from the Alzheimer's Disease Neuroimaging Initiative with available CSF (n = 274) and/or 3T-MRI (n = 168) and/or a FDG-PET analyses (n = 328) were selected. CSF amyloid-β1-42 (Aβ1-42), total-tau (t-tau) and phospho-tau (p-tau181p) levels were measured by Luminex assays. We analyzed the APOE-by-sex interaction on the CSF biomarkers in an analysis of covariance (ANCOVA). FDG uptake was analyzed by SPM8 and cortical thickness (CTh) was measured by FreeSurfer. FDG and CTh difference maps were derived from interaction and group analyses. RESULTS: APOE4 carriers had lower CSF Aβ1-42 and higher CSF p-tau181p values than non-carriers, but there was no APOE-by-sex interaction on CSF biomarkers. The APOE-by-sex interaction on brain metabolism and brain structure was significant. Sex stratification showed that female APOE4 carriers presented widespread brain hypometabolism and cortical thinning compared to female non-carriers whereas male APOE4 carriers showed only a small cluster of hypometabolism and regions of cortical thickening compared to male non-carriers. CONCLUSIONS: The impact of APOE4 on brain metabolism and structure is modified by sex. Female APOE4 carriers show greater hypometabolism and atrophy than male carriers. This APOE-by-sex interaction should be considered in clinical trials in preclinical AD where APOE4 status is a selection criterion.
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It is part of: Oncotarget, 2015, vol. 6, num. 29, p. 26663-26674
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ISSN: 1949-2553
Appears in Collections:Articles publicats en revistes (Biomedicina)

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