title: Apolipoprotein E epsilon 4 allele is associated with ventricular expansion rate and surface morphology in dementia and normal aging.
abstract: The apolipoprotein E epsilon 4 allele (ApoE-ε4) is the strongest known genetic risk factor for late onset Alzheimer's disease. Expansion of the lateral ventricles occurs with normal aging, but dementia accelerates this process. Brain structure and function depend on ApoE genotype not just for Alzheimer's disease patients but also in healthy elderly individuals, and even in asymptomatic young individuals. Therefore, we hypothesized that the ApoE-ε4 allele is associated with altered patterns of longitudinal ventricular expansion, in dementia and normal aging. We tested this hypothesis in a large sample of elderly participants, using a linear discriminant analysis-based approach. Carrying more ApoE-ε4 alleles was associated with faster ventricular expansion bilaterally and with regional patterns of lateral ventricle morphology at 1- and 2-year follow up, after controlling for sex, age, and dementia status. ApoE genotyping is considered critical in clinical trials of Alzheimer's disease. These findings, combined with earlier investigations showing that ApoE is also directly implicated in other conditions, suggest that the selective enrollment of ApoE-ε4 carriers may empower clinical trials of other neurological disorders.
authors.affiliation: Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: Florence F
authors.initials: FF
authors.lastname: Roussotte
authors.affiliation: Department of Psychiatry, Semel Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; Imaging Genetics Center, USC Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Boris A
authors.initials: BA
authors.lastname: Gutman
authors.affiliation: Department of Psychiatry, Semel Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; Imaging Genetics Center, USC Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Madsen
authors.affiliation: Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: John B
authors.initials: JB
authors.lastname: Colby
authors.affiliation: Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Narr
authors.affiliation: Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; Department of Psychiatry, Semel Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; Imaging Genetics Center, USC Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Department of Neurology, USC Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Department of Psychiatry, USC Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Department of Radiology, USC Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Department of Engineering, USC Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Department of Pediatrics, USC Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Department of Ophthalmology, USC Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. Electronic address: pthomp@usc.edu.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Thompson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics* / Q000473:pathology*; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology*; D053327:Apolipoprotein E4 / Q000235:genetics*; D002552:Cerebral Ventricles / Q000473:pathology*; D060825:Cognitive Dysfunction / Q000235:genetics / Q000473:pathology; D016208:Databases, Factual; D003704:Dementia / Q000235:genetics / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D012307:Risk Factors; D013997:Time Factors
chemical_list: D053327:Apolipoprotein E4
keywords: ApoE; Dementia; Neuroimaging genetics; Structural MRI; Ventricular expansion