APOE-by-sex interactions on brain structure and metabolism in healthy elderly controls

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). Cross-sectional study. HC from the...

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Bibliographic Details
Published in:Oncotarget 2015-09, Vol.6 (29), p.26663-26674
Main Authors: Sampedro, Frederic, Vilaplana, Eduard, de Leon, Mony J, Alcolea, Daniel, Pegueroles, Jordi, Montal, Victor, Carmona-Iragui, María, Sala, Isabel, Sánchez-Saudinos, María-Belén, Antón-Aguirre, Sofía, Morenas-Rodríguez, Estrella, Camacho, Valle, Falcón, Carles, Pavía, Javier, Ros, Domènec, Clarimón, Jordi, Blesa, Rafael, Lleó, Alberto, Fortea, Juan
Format: Article
Language:English
Subjects:
Aged
Aged, 80 and over
Aging
Alzheimer Disease - genetics
Alzheimer's disease
Apolipoprotein E4 - cerebrospinal fluid
Apolipoprotein E4 - genetics
Atrophy
Biomarkers - cerebrospinal fluid
Blood lipids
Brain - diagnostic imaging
Brain - metabolism
Brain - pathology
Cross-Sectional Studies
Envelliment
Female
Genetic diseases
Genetic Predisposition to Disease
Genotype
Healthy Volunteers
Heterozygote
Humans
Lípids de la sang
Magnetic Resonance Imaging
Malaltia d'Alzheimer
Malalties hereditàries
Male
Middle Aged
Positron-Emission Tomography
Proteins
Proteïnes
Research Paper: Gerotarget (Focus on Aging)
Sex Factors
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Summary: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). 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. 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. 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.
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.5185