Population-based analysis of cholesteryl ester transfer protein identifies association between I405V and cognitive decline: The cache county study

Caitlin Lythgoe; Ammon Perkes; Michael Peterson; Cameron Schmutz; Maegan Leary; Mark T.W. Ebbert; Perry G. Ridge; Maria C. Norton; Jo Ann T. Tschanz; Ronald G. Munger; Christopher D. Corcoran; John S.K. Kauwe

doi:10.1016/j.neurobiolaging.2014.08.022

Population-based analysis of cholesteryl ester transfer protein identifies association between I405V and cognitive decline: The cache county study

Caitlin Lythgoe, Ammon Perkes, Michael Peterson, Cameron Schmutz, Maegan Leary, Mark T.W. Ebbert, Perry G. Ridge, Maria C. Norton, Jo Ann T. Tschanz, Ronald G. Munger, Christopher D. Corcoran, John S.K. Kauwe

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

Cholesterol has been implicated in the pathogenesis of late-onset Alzheimer's disease (LOAD) and the cholesteryl ester transfer protein (CETP) is critical to cholesterol regulation within the cell, making CETP an Alzheimer's disease candidate gene. Several studies have suggested that CETP I405V (rs5882) is associated with cognitive function and LOAD risk, but findings vary and most studies have been conducted using relatively small numbers of samples. To test whether this variant is involved in cognitive function and LOAD progression, we genotyped 4486 subjects with up to 12 years of longitudinal cognitive assessment. Analyses revealed an average 0.6-point decrease per year in the rate of cognitive decline for each additional valine (p < 0.011). We failed to detect the association between CETP I405V and LOAD status (p < 0.28). We conclude that CETP I405V is associated with preserved cognition over time but is not associated with LOAD status.

Original language	English
Pages (from-to)	547.e1-547.e3
Journal	Neurobiology of Aging
Volume	36
Issue number	1
DOIs	https://doi.org/10.1016/j.neurobiolaging.2014.08.022
State	Published - Jan 1 2015

Bibliographical note

Funding Information:
This work was supported by the Alzheimer’s Association ( MNIRG-11-205368 ), the BYU Gerontology Program and the National Institutes of Health ( R01-AG11380 , R01- AG021136 , P30-NS069329-01 , R01-AG042611 ). The Institutional Review Boards of each appropriate institution approved sample and data collection. The authors gratefully acknowledge the individuals who participated in this study without whom this work would not have been possible.

Publisher Copyright:
© 2015 Elsevier Inc.

Keywords

Alzheimer's
Alzheimer's disease
CETP
Cache county
Cognitive decline
I405V

ASJC Scopus subject areas

Neuroscience (all)
Aging
Developmental Biology
Clinical Neurology
Geriatrics and Gerontology

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10.1016/j.neurobiolaging.2014.08.022

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Lythgoe, C., Perkes, A., Peterson, M., Schmutz, C., Leary, M., Ebbert, M. T. W., Ridge, P. G., Norton, M. C., Tschanz, J. A. T., Munger, R. G., Corcoran, C. D., & Kauwe, J. S. K. (2015). Population-based analysis of cholesteryl ester transfer protein identifies association between I405V and cognitive decline: The cache county study. Neurobiology of Aging, 36(1), 547.e1-547.e3. https://doi.org/10.1016/j.neurobiolaging.2014.08.022

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title = "Population-based analysis of cholesteryl ester transfer protein identifies association between I405V and cognitive decline: The cache county study",

abstract = "Cholesterol has been implicated in the pathogenesis of late-onset Alzheimer's disease (LOAD) and the cholesteryl ester transfer protein (CETP) is critical to cholesterol regulation within the cell, making CETP an Alzheimer's disease candidate gene. Several studies have suggested that CETP I405V (rs5882) is associated with cognitive function and LOAD risk, but findings vary and most studies have been conducted using relatively small numbers of samples. To test whether this variant is involved in cognitive function and LOAD progression, we genotyped 4486 subjects with up to 12 years of longitudinal cognitive assessment. Analyses revealed an average 0.6-point decrease per year in the rate of cognitive decline for each additional valine (p < 0.011). We failed to detect the association between CETP I405V and LOAD status (p < 0.28). We conclude that CETP I405V is associated with preserved cognition over time but is not associated with LOAD status.",

keywords = "Alzheimer's, Alzheimer's disease, CETP, Cache county, Cognitive decline, I405V",

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note = "Funding Information: This work was supported by the Alzheimer{\textquoteright}s Association ( MNIRG-11-205368 ), the BYU Gerontology Program and the National Institutes of Health ( R01-AG11380 , R01- AG021136 , P30-NS069329-01 , R01-AG042611 ). The Institutional Review Boards of each appropriate institution approved sample and data collection. The authors gratefully acknowledge the individuals who participated in this study without whom this work would not have been possible. Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",

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Lythgoe, C, Perkes, A, Peterson, M, Schmutz, C, Leary, M, Ebbert, MTW, Ridge, PG, Norton, MC, Tschanz, JAT, Munger, RG, Corcoran, CD & Kauwe, JSK 2015, 'Population-based analysis of cholesteryl ester transfer protein identifies association between I405V and cognitive decline: The cache county study', Neurobiology of Aging, vol. 36, no. 1, pp. 547.e1-547.e3. https://doi.org/10.1016/j.neurobiolaging.2014.08.022

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T1 - Population-based analysis of cholesteryl ester transfer protein identifies association between I405V and cognitive decline

T2 - The cache county study

AU - Lythgoe, Caitlin

AU - Perkes, Ammon

AU - Peterson, Michael

AU - Schmutz, Cameron

AU - Leary, Maegan

AU - Ebbert, Mark T.W.

AU - Ridge, Perry G.

AU - Norton, Maria C.

AU - Tschanz, Jo Ann T.

AU - Munger, Ronald G.

AU - Corcoran, Christopher D.

AU - Kauwe, John S.K.

N1 - Funding Information: This work was supported by the Alzheimer’s Association ( MNIRG-11-205368 ), the BYU Gerontology Program and the National Institutes of Health ( R01-AG11380 , R01- AG021136 , P30-NS069329-01 , R01-AG042611 ). The Institutional Review Boards of each appropriate institution approved sample and data collection. The authors gratefully acknowledge the individuals who participated in this study without whom this work would not have been possible. Publisher Copyright: © 2015 Elsevier Inc.

PY - 2015/1/1

Y1 - 2015/1/1

N2 - Cholesterol has been implicated in the pathogenesis of late-onset Alzheimer's disease (LOAD) and the cholesteryl ester transfer protein (CETP) is critical to cholesterol regulation within the cell, making CETP an Alzheimer's disease candidate gene. Several studies have suggested that CETP I405V (rs5882) is associated with cognitive function and LOAD risk, but findings vary and most studies have been conducted using relatively small numbers of samples. To test whether this variant is involved in cognitive function and LOAD progression, we genotyped 4486 subjects with up to 12 years of longitudinal cognitive assessment. Analyses revealed an average 0.6-point decrease per year in the rate of cognitive decline for each additional valine (p < 0.011). We failed to detect the association between CETP I405V and LOAD status (p < 0.28). We conclude that CETP I405V is associated with preserved cognition over time but is not associated with LOAD status.

AB - Cholesterol has been implicated in the pathogenesis of late-onset Alzheimer's disease (LOAD) and the cholesteryl ester transfer protein (CETP) is critical to cholesterol regulation within the cell, making CETP an Alzheimer's disease candidate gene. Several studies have suggested that CETP I405V (rs5882) is associated with cognitive function and LOAD risk, but findings vary and most studies have been conducted using relatively small numbers of samples. To test whether this variant is involved in cognitive function and LOAD progression, we genotyped 4486 subjects with up to 12 years of longitudinal cognitive assessment. Analyses revealed an average 0.6-point decrease per year in the rate of cognitive decline for each additional valine (p < 0.011). We failed to detect the association between CETP I405V and LOAD status (p < 0.28). We conclude that CETP I405V is associated with preserved cognition over time but is not associated with LOAD status.

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KW - Cognitive decline

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SN - 0197-4580

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SP - 547.e1-547.e3

JO - Neurobiology of Aging

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IS - 1

ER -

Population-based analysis of cholesteryl ester transfer protein identifies association between I405V and cognitive decline: The cache county study

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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