CETP Genotype Modifies the Effect of Apolipoprotein ε4 on Memory Decline in Older Adults

Details

• Alternative Title:
  Neurobiol Aging
• Personal Author:
  Sundermann, EE ; Wang, C ; Katz, M ; Zimmerman, ME ; Derby, CA ; Hall, CB ; Ozelius, LJ ; Lipton, RB
• Description:
  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.
• Subjects:
  Aged Aged, 80 And Over Alzheimer Disease Apolipoproteins E Cholesterol Ester Transfer Proteins Epistasis, Genetic Female Gene Dosage Heterozygote Homozygote Humans Male Memory, Episodic Memory Disorders Polymorphism, Single Nucleotide Risk Factors

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• Source:
  Neurobiol Aging. 41:200.e7-200.e12.
• Pubmed ID:
  27033407
• Pubmed Central ID:
  PMC5586214
• Document Type:
  Journal Article
• Funding:
  R01 AG022374/AG/NIA NIH HHS/United States ; R21 AG036935/AG/NIA NIH HHS/United States ; UL1 RR025750/RR/NCRR NIH HHS/United States ; R01 AG039409/AG/NIA NIH HHS/United States ; R03 AG045474/AG/NIA NIH HHS/United States ; R01 AG034119/AG/NIA NIH HHS/United States ; R01 HL094581/HL/NHLBI NIH HHS/United States ; U10 OH008242/OH/NIOSH CDC HHS/United States ; R01 AG042595/AG/NIA NIH HHS/United States ; 1UL1TR001073/TR/NCATS NIH HHS/United States ; U01 OH010411/OH/NIOSH CDC HHS/United States ; R01 AG039330/AG/NIA NIH HHS/United States ; R01 AG012101/AG/NIA NIH HHS/United States ; P01 AG03949/AG/NIA NIH HHS/United States ; R01 AG034087/AG/NIA NIH HHS/United States ; R01 AG022092/AG/NIA NIH HHS/United States ; R01 AG036921/AG/NIA NIH HHS/United States ; R01 AG038651/AG/NIA NIH HHS/United States ; K23 NS047256/NS/NINDS NIH HHS/United States ; U01 AG012535/AG/NIA NIH HHS/United States ; UL1 TR001073/TR/NCATS NIH HHS/United States ; R01 NS081282/NS/NINDS NIH HHS/United States ; P01 AG027734/AG/NIA NIH HHS/United States ; R01 AG025119/AG/NIA NIH HHS/United States ; U01 OH010412/OH/NIOSH CDC HHS/United States ; K23 AG030857/AG/NIA NIH HHS/United States ; P01 AG003949/AG/NIA NIH HHS/United States ; P01 NS037409/NS/NINDS NIH HHS/United States ; P30 CA013330/CA/NCI NIH HHS/United States ; R01 DC011805/DC/NIDCD NIH HHS/United States
• Volume:
  41
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:d43d91a17d4d53fc4b975f54e323366d6bfe9e4893fce67a187b7730abd9aedc
• Download URL:
  https://stacks.cdc.gov/view/cdc/48025/cdc_48025_DS1.pdf
• File Type:
  [PDF - 628.17 KB ]