title: APOE-epsilon4 and aging of medial temporal lobe gray matter in healthy adults older than 50 years.
abstract: Atrophy of the hippocampus and surrounding temporal regions occurs in Alzheimer's disease (AD). APOE ε4, the major genetic risk factor for late-onset AD, has been associated with smaller volume in these regions before amyloidosis can be detected by AD biomarkers. To examine APOE ε4 effects in relation to aging, we performed a longitudinal magnetic resonance imaging study involving cognitively normal adults (25 APOE ε4 carriers and 31 ε3 homozygotes), initially aged 51-75 years. We used growth curve analyses, which can provide information about APOE ε4-related differences initially and later in life. Hippocampal volume was the primary outcome; nearby medial temporal regions were secondary outcomes. Brain-derived neurotrophic factor, val66met was a secondary covariate. APOE ε4 carriers had significantly smaller initial hippocampal volumes than ε3 homozygotes. Rate of hippocampal atrophy was not greater in the APOE ε4 group, although age-related atrophy was detected in the overall sample. The findings add to the growing evidence that effects of APOE ε4 on hippocampal size begin early in life, underscoring the importance of early interventions to increase reserve.
authors.affiliation: Veterans Affairs Palo Alto Health Care System, Sierra-Pacific MIRECC, Palo Alto CA, USA; Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA. Electronic address: joyt@stanford.edu.
authors.forename: Joy L
authors.initials: JL
authors.lastname: Taylor
authors.affiliation: Veterans Affairs Palo Alto Health Care System, Sierra-Pacific MIRECC, Palo Alto CA, USA; Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Blake K
authors.initials: BK
authors.lastname: Scanlon
authors.affiliation: Veterans Affairs Palo Alto Health Care System, Sierra-Pacific MIRECC, Palo Alto CA, USA; Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Farrell
authors.affiliation: Veterans Affairs Palo Alto Health Care System, Sierra-Pacific MIRECC, Palo Alto CA, USA; Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Hernandez
authors.affiliation: Veterans Affairs Palo Alto Health Care System, Sierra-Pacific MIRECC, Palo Alto CA, USA; Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Maheen M
authors.initials: MM
authors.lastname: Adamson
authors.affiliation: Veterans Affairs Palo Alto Health Care System, Sierra-Pacific MIRECC, Palo Alto CA, USA; Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: J Wesson
authors.initials: JW
authors.lastname: Ashford
authors.affiliation: Veterans Affairs Palo Alto Health Care System, Sierra-Pacific MIRECC, Palo Alto CA, USA; Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Art
authors.initials: A
authors.lastname: Noda
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Greer M
authors.initials: GM
authors.lastname: Murphy
authors.affiliation: Department of Veterans Affairs Medical Center, Center for Imaging of Neurodegenerative Diseases, San Francisco, CA, USA; Department of Radiology, University of California, San Francisco, CA, USA.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Weiner
mesh_terms: D000368:Aged; D000375:Aging / Q000473:pathology*; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology*; D053327:Apolipoprotein E4 / Q000235:genetics*; D001284:Atrophy; D019208:Brain-Derived Neurotrophic Factor; D004268:DNA-Binding Proteins; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D060588:LIM Domain Proteins; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D012307:Risk Factors; D013702:Temporal Lobe / Q000473:pathology
chemical_list: D053327:Apolipoprotein E4; D019208:Brain-Derived Neurotrophic Factor; D004268:DNA-Binding Proteins; D060588:LIM Domain Proteins; C486247:PDLIM4 protein, human
keywords: Aging; Alzheimer's disease; Apolipoprotein E4; Brain-derived neurotrophic factor; Hippocampus; Longitudinal studies; Magnetic resonance imaging