@article{e5c9aa9e36534c789471fa9e47182236,
title = "Cholesteryl ester transfer protein genotype modifies the effect of apolipoprotein ε4 on memory decline in older adults",
abstract = "Apolipoprotein ε4 (ApoE4) is a strong genetic risk factor for sporadic Alzheimer's disease and memory decline in older adults. A single-nucleotide polymorphism in the cholesteryl ester transfer protein (CETP) gene (isoleucine to valine; V405) is associated with slower memory decline and a lower risk of Alzheimer's disease. As both genes regulate cholesterol, we hypothesized that the favorable CETPV405 allele may buffer the effect of ApoE4 on memory decline in older adults. Using linear regression, we examined the interactive effect of ApoE4 by CETPV405 on memory decline among 909 community-dwelling, nondemented, older adults (≥70 years) from the Einstein Aging Study. Episodic memory was measured using the picture version of the Free and Cued Selective Reminding Test with immediate recall (pFCSRT+IR). There was a significant ApoE × CETP interaction on decline in pFCSRT+IR scores (p = 0.01). ApoE4 carriers experienced faster decline than noncarriers among CETPI405I homozygotes (p = 0.007) and in CETPI405V heterozygotes (p = 0.015) but not in CETPV405V homozygotes (p = 0.614). Results suggest that the CETPV405 allele buffers ApoE4-associated memory decline in a gene dose-dependent manner.",
keywords = "ApoE ε4, CETP, Gene-gene interaction, I405V, Memory decline",
author = "Sundermann, {Erin Elizabeth} and Cuiling Wang and Mindy Katz and Zimmerman, {Molly E.} and Derby, {Carol A.} and Hall, {Charles B.} and Ozelius, {Laurie J.} and Lipton, {Richard B.}",
note = "Funding Information: Erin Sundermann reports no disclosures. Cuiling Wang receives research support from NIH P01 AG039409 (investigator), R01 AG039330 (investigator), R01 AG036921 (investigator), R01 HL094581 (investigator), and Bristol-Myers Squibb. Mindy J. Katz receives research support from NIH-NIA P01 AG027734 (investigator), R01 AG022374 (investigator), NIH-NIA R01 AG034119 (investigator), NIH-NIA P01 AG039409 (investigator), NIH-NIA AG038651 (investigator), R01AG042595 (investigator), and R03AG045474 (principal investigator). Molly E. Zimmerman receives research support from the NIH P01 AG03949 (coinvestigator). Carol A. Derby receives research support from NIH P01 AG039409 (project leader), P01AG027734 (coinvestigator), 5R01 AG22374 (site principal investigator), 2U01AG012535-16 (principal investigator), NCRR 5UL1RR025750-03 (investigator), Bristol-Myers Squibb, and the S and L Marx Foundation. Charles B. Hall has received research support from the National Institute of Aging (P01 AG03949, P01 AG027734, R01 AG022092, R01 AG034087, R01 AG034119, R21 AG036935), the National Center for Research Resources (1-UL1-RR025750-01), the National Cancer Institute (P30 CA13330-35), the National Institute of Occupational Safety and Health (5-U011O-OH008242, U01 OH010411, U01 OH010412, and contracts 200-2011-39,378 and 200-2011–39,489), and Endo Pharmaceuticals, has consulted to research projects at the University of Connecticut Health Center, is and has been a member of Data and Safety Monitoring Committees at Columbia University, received honoraria from Washington University St. Louis and from Oregon Health and Science University, has received travel funding from Washington University St. Louis, Yale University, Oregon Health and Science University, and the University of Victoria, and is a member of the American Statistical Association Media Experts Panel. Laurie J. Ozelius received research funding from NIH (DC011805, NS037409, NS081282) and Foundation for Dystonia Research, she also receives patent royalties from Athena Diagnostics. Richard B. Lipton receives research support from the NIH: PO1 AG003949 (program director), PO1AG027734 (project leader), RO1AG025119 (investigator), RO1AG022374-06A2 (investigator), RO1AG034119 (investigator), RO1AG12101 (investigator), K23AG030857 (mentor), K23NS05140901A1 (mentor), and K23NS47256 (mentor), the National Headache Foundation, and the Migraine Research Fund; serves on the editorial boards of Neurology and Cephalalgia and as senior advisor to Headache, has reviewed for the NIA and NINDS, holds stock options in eNeura Therapeutics (a company without commercial products); serves as consultant, advisory board member, or has received honoraria from: Alder, Allergan, American Headache Society, Autonomic Technologies, Avanir, Boston Scientific, Bristol Myers Squibb, Colucid, Dr. Reddy's, Electrocore, Eli Lilly, Endo, eNeura Therapeutics, Informa, Labrys, Merck, Novartis, Teva, Vedanta. Funding Information: This research was supported by the Einstein Aging Study (PO1 AG03949) from the National Institutes on Aging program; the National Institutes of Health CTSA ( 1UL1TR001073 ) from the National Center for Advancing Translational Sciences , the Sylvia and Lenard Marx Foundation , and the Czap Foundation . The contents of this article are solely the responsibility of the authors and do not necessary represent the official view of the NCRR or NIH. Role of the sponsor: the National Institutes on Aging had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the article. ",
year = "2016",
month = may,
day = "1",
doi = "10.1016/j.neurobiolaging.2016.02.006",
language = "English (US)",
volume = "41",
pages = "200.e7--200.e12",
journal = "Neurobiology of Aging",
issn = "0197-4580",
publisher = "Elsevier Inc.",
}