title: Gray matter network associated with risk for Alzheimer's disease in young to middle-aged adults.
abstract: The apolipoprotein E (APOE) ε4 allele increases the risk for late-onset Alzheimer's disease (AD) and age-related cognitive decline. We investigated whether ε4 carriers show reductions in gray matter volume compared with ε4 non-carriers decades before the potential onset of AD dementia or healthy cognitive aging. Fourteen cognitively normal ε4 carriers, aged 26 to 45 years, were compared with 10 age-matched, ε4 non-carriers using T1-weighted volumetric magnetic resonance imaging (MRI) scans. All had reported first- or second-degree family histories of dementia. Group differences in gray matter were tested using voxel-based morphometry (VBM) and a multivariate model of regional covariance, the Scaled Subprofile Model (SSM). A combination of the first two SSM MRI gray matter patterns distinguished the APOE ε4 carriers from non-carriers. This combined pattern showed gray matter reductions in bilateral dorsolateral and medial frontal, anterior cingulate, parietal, and lateral temporal cortices with covarying relative increases in cerebellum, occipital, fusiform, and hippocampal regions. With these gray matter differences occurring decades before the potential onset of dementia or cognitive aging, the results suggest longstanding, gene-associated differences in brain morphology that may lead to preferential vulnerability for the later effects of late-onset AD or healthy brain aging.
authors.affiliation: Department of Psychology, University of Arizona, Tucson, AZ 85721, USA. gene.alexander@arizona.edu
authors.forename: Gene E
authors.initials: GE
authors.lastname: Alexander
authors.forename: Kaitlin L
authors.initials: KL
authors.lastname: Bergfield
authors.forename: Kewei
authors.initials: K
authors.lastname: Chen
authors.forename: Eric M
authors.initials: EM
authors.lastname: Reiman
authors.forename: Krista D
authors.initials: KD
authors.lastname: Hanson
authors.forename: Lan
authors.initials: L
authors.lastname: Lin
authors.forename: Daniel
authors.initials: D
authors.lastname: Bandy
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Caselli
authors.forename: James R
authors.initials: JR
authors.lastname: Moeller
mesh_terms: D000328:Adult; D000544:Alzheimer Disease / Q000150:complications / Q000235:genetics / Q000473:pathology*; D053327:Apolipoprotein E4 / Q000235:genetics; D001921:Brain / Q000473:pathology*; D016022:Case-Control Studies; D003072:Cognition Disorders / Q000209:etiology; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000473:pathology*; D009483:Neuropsychological Tests; D012044:Regression Analysis
chemical_list: D053327:Apolipoprotein E4