Presence of ApoE ε4 Allele Associated with Thinner Frontal Cortex in Middle Age
Year: 2011
Type: article
Study design: Observational Study
Abstract: The presence of an ApoE ε4 allele (ε4+) increases the risk of developing Alzheimer's disease (AD). Previous studies support an adverse relationship between ε4+ status and brain structure and function in mild cognitive impairment and AD; in contrast, the presence of an ε2 allele may be protective. Whether these findings reflect disease-related effects or pre-existing endophenotypes, however, remains unclear. The present study examined the influence of ApoE allele status on brain structure solely during middle-age in a large, national sample. Participants were 482 men, ages 51-59, from the Vietnam Era Twin Study of Aging (VETSA). T1-weighted images were used in volumetric segmentation and cortical surface reconstruction methods to measure regional volume and thickness. Primary linear mixed effects models predicted structural measures with ApoE status (ε3/3, ε2/3, ε3/4) and control variables for effects of site, non-independence of twin data, age, and average cranial vault or cortical thickness. Relative to the ε3/3 group, the ε3/4 group demonstrated significantly thinner cortex in superior frontal and left rostral and right caudal midfrontal regions; there were no significant effects of ε4 status on any temporal lobe measures. The ε2/3 group demonstrated significantly thicker right parahippocampal cortex relative to the ε3/3 group. The ApoE ε4 allele may influence cortical thickness in frontal areas, which are later developing regions thought to be more susceptible to the natural aging process. Previous conflicting findings for mesial temporal regions may be driven by the inclusion of older individuals, who may evidence preclinical manifestations of disease, and by unexamined moderators of ε4-related effects. The presence of the ε2 allele was related to thicker cortex, supporting a protective role. Ongoing follow-up of the VETSA sample may shed light on the potential for age- and disease-related mediation of the influence of ApoE allele status.
Source: Journal of Alzheimer s Disease
Authors: Christine Fennema-Notestine, Matthew S. Panizzon, Wesley R. Thompson, Chi-Hua Chen, Lisa T. Eyler, Bruce Fischl, Carol E. Franz, Michael D. Grant, Amy J. Jak, Terry L. Jernigan, Michael J. Lyons, Michael C. Neale, Larry J. Seidman, Ming T. Tsuang, Hong Xian, Anders M. Dale, William S. Kremen
Institutions: University of California San Diego, VA San Diego Healthcare System, Harvard University, Massachusetts General Hospital, MIT Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Boston University, Virginia Commonwealth University, Virginia Commonwealth University Medical Center, Washington University in St. Louis
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: U.S. Department of Defense, U.S. Department of Veterans Affairs, Ellison Medical Foundation, Temple University, National Institutes of Health, University of California, San Diego, National Institute on Aging, National Institute of Neurological Disorders and Stroke, National Institute of Biomedical Imaging and Bioengineering, National Center for Research Resources
Awards: G1923530831, Morphometry Biomedical Informatics Research Network, The VETSA Longitudinal Twin Study of Cortisol and Aging, Inferring in Vivo Cytoarchitectural Borders in the Medial Temporal Lobe, The VETSA Longitudinal MRI Twin Study of Aging, Center for Functional Imaging Technologies, Software Tools for Automated Modeling of White Matter Fascicles from Diffusion MR, The VETSA Longitudinal Twin Study of Cognition and Aging, Tools for Analyzing Cortical Structure and Connectivity, The VETSA longitudinal twin study of cognition and aging
OpenAlex ID: W2146839662