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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 200.e7-200.e12 |
| Journal | Neurobiology of Aging |
| Volume | 41 |
| DOIs | |
| State | Published - May 1 2016 |
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Keywords
- ApoE ε4
- CETP
- Gene-gene interaction
- I405V
- Memory decline
ASJC Scopus subject areas
- Clinical Neurology
- Neuroscience(all)
- Aging
- Developmental Biology
- Geriatrics and Gerontology
Cite this
Cholesteryl ester transfer protein genotype modifies the effect of apolipoprotein ε4 on memory decline in older adults. / Sundermann, Erin Elizabeth; Wang, Cuiling; Katz, Mindy Joy; Zimmerman, Molly E.; Derby, Carol A.; Hall, Charles B.; Ozelius, Laurie J.; Lipton, Richard B.
In: Neurobiology of Aging, Vol. 41, 01.05.2016, p. 200.e7-200.e12.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Cholesteryl ester transfer protein genotype modifies the effect of apolipoprotein ε4 on memory decline in older adults
AU - Sundermann, Erin Elizabeth
AU - Wang, Cuiling
AU - Katz, Mindy Joy
AU - Zimmerman, Molly E.
AU - Derby, Carol A.
AU - Hall, Charles B.
AU - Ozelius, Laurie J.
AU - Lipton, Richard B.
PY - 2016/5/1
Y1 - 2016/5/1
N2 - 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.
AB - 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.
KW - ApoE ε4
KW - CETP
KW - Gene-gene interaction
KW - I405V
KW - Memory decline
UR - http://www.scopus.com/inward/record.url?scp=84963594599&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84963594599&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2016.02.006
DO - 10.1016/j.neurobiolaging.2016.02.006
M3 - Article
VL - 41
SP - 200.e7-200.e12
JO - Neurobiology of Aging
JF - Neurobiology of Aging
SN - 0197-4580
ER -