title: APOE-by-sex interactions on brain structure and metabolism in healthy elderly controls.
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.
authors.affiliation: Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau - Biomedical Research Institute Sant Pau - Universitat Autònoma de Barcelona, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, CIBERNED, Madrid, Spain.|Nuclear Medicine Department, Hospital de la Santa Creu i Sant Pau - Biomedical Research Institute Sant Pau - Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Frederic
authors.initials: F
authors.lastname: Sampedro
authors.affiliation: Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau - Biomedical Research Institute Sant Pau - Universitat Autònoma de Barcelona, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, CIBERNED, Madrid, Spain.
authors.forename: Eduard
authors.initials: E
authors.lastname: Vilaplana
authors.affiliation: New York University School of Medicine, New York, NY, USA.
authors.forename: Mony J
authors.initials: MJ
authors.lastname: de Leon
authors.affiliation: Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau - Biomedical Research Institute Sant Pau - Universitat Autònoma de Barcelona, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, CIBERNED, Madrid, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Alcolea
authors.affiliation: Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau - Biomedical Research Institute Sant Pau - Universitat Autònoma de Barcelona, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, CIBERNED, Madrid, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Pegueroles
authors.affiliation: Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau - Biomedical Research Institute Sant Pau - Universitat Autònoma de Barcelona, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, CIBERNED, Madrid, Spain.
authors.forename: Victor
authors.initials: V
authors.lastname: Montal
authors.affiliation: Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau - Biomedical Research Institute Sant Pau - Universitat Autònoma de Barcelona, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, CIBERNED, Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Carmona-Iragui
authors.affiliation: Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau - Biomedical Research Institute Sant Pau - Universitat Autònoma de Barcelona, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, CIBERNED, Madrid, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Sala
authors.affiliation: Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau - Biomedical Research Institute Sant Pau - Universitat Autònoma de Barcelona, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, CIBERNED, Madrid, Spain.
authors.forename: María-Belén
authors.initials: MB
authors.lastname: Sánchez-Saudinos
authors.affiliation: Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau - Biomedical Research Institute Sant Pau - Universitat Autònoma de Barcelona, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, CIBERNED, Madrid, Spain.
authors.forename: Sofía
authors.initials: S
authors.lastname: Antón-Aguirre
authors.affiliation: Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau - Biomedical Research Institute Sant Pau - Universitat Autònoma de Barcelona, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, CIBERNED, Madrid, Spain.
authors.forename: Estrella
authors.initials: E
authors.lastname: Morenas-Rodríguez
authors.affiliation: Nuclear Medicine Department, Hospital de la Santa Creu i Sant Pau - Biomedical Research Institute Sant Pau - Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Valle
authors.initials: V
authors.lastname: Camacho
authors.affiliation: Unitat de Biofísica i Bioenginyeria, Departament de Ciències Fisiològiques I, Facultat de Medicina, Universitat de Barcelona - IDIBAPS, Barcelona, Spain.|Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine - CIBER-BBN, Barcelona, Spain.
authors.forename: Carles
authors.initials: C
authors.lastname: Falcón
authors.affiliation: Nuclear Medicine Department. Hospital Clínic de Barcelona, Barcelona, Spain.|Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine - CIBER-BBN, Barcelona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Pavía
authors.affiliation: Unitat de Biofísica i Bioenginyeria, Departament de Ciències Fisiològiques I, Facultat de Medicina, Universitat de Barcelona - IDIBAPS, Barcelona, Spain.|Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine - CIBER-BBN, Barcelona, Spain.
authors.forename: Domènec
authors.initials: D
authors.lastname: Ros
authors.affiliation: Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau - Biomedical Research Institute Sant Pau - Universitat Autònoma de Barcelona, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, CIBERNED, Madrid, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Clarimón
authors.affiliation: Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau - Biomedical Research Institute Sant Pau - Universitat Autònoma de Barcelona, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, CIBERNED, Madrid, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Blesa
authors.affiliation: Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau - Biomedical Research Institute Sant Pau - Universitat Autònoma de Barcelona, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, CIBERNED, Madrid, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Lleó
authors.affiliation: Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau - Biomedical Research Institute Sant Pau - Universitat Autònoma de Barcelona, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, CIBERNED, Madrid, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Fortea
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D000544:Alzheimer Disease / Q000235:genetics; D053327:Apolipoprotein E4 / Q000134:cerebrospinal fluid* / Q000235:genetics*; D001284:Atrophy; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D003430:Cross-Sectional Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D064368:Healthy Volunteers; D006579:Heterozygote; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D012737:Sex Factors
chemical_list: D053327:Apolipoprotein E4; D015415:Biomarkers
keywords: APOE; Alzheimer’s disease; Gerotarget; MRI; PET-FDG; aging