• Open Access

The CETP I405V polymorphism is associated with an increased risk of Alzheimer’s disease

Authors

  • Lei Yu,

    1. Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago, IL, USA
    2. Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA
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  • Joshua M. Shulman,

    1. Program in Translational NeuroPsychiatric Genomics, Departments of Neurology & Psychiatry, Institute for the Neurosciences, Brigham and Women’s Hospital, Boston, MA, USA
    2. Harvard Medical School, Boston, MA, USA
    3. Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA
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  • Lori Chibnik,

    1. Program in Translational NeuroPsychiatric Genomics, Departments of Neurology & Psychiatry, Institute for the Neurosciences, Brigham and Women’s Hospital, Boston, MA, USA
    2. Harvard Medical School, Boston, MA, USA
    3. Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA
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  • Sue Leurgans,

    1. Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago, IL, USA
    2. Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA
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  • Julie A. Schneider,

    1. Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago, IL, USA
    2. Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA
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  • Philip L. De Jager,

    1. Program in Translational NeuroPsychiatric Genomics, Departments of Neurology & Psychiatry, Institute for the Neurosciences, Brigham and Women’s Hospital, Boston, MA, USA
    2. Harvard Medical School, Boston, MA, USA
    3. Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA
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  • David A. Bennett

    1. Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago, IL, USA
    2. Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA
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Lei Yu, PhD, Rush Alzheimer’s Disease Center, Department of Neurological Science, Rush University Medical Center, 600 South Paulina Street, Suite 1020B, Chicago, IL 60612, USA. Tel.: 312 942 0543; fax: 312 942 2297; e-mail: lei_yu@rush.edu

Summary

The cholesteryl ester transfer protein (CETP) gene plays an essential role in regulating cholesterol homeostasis and is a candidate susceptibility gene for late-onset Alzheimer’s disease (AD). Recent finding suggests that the CETP I405V polymorphism (rs5882) is associated with a slower rate of memory decline and a lower risk of incident dementia. Using data from two ongoing epidemiologic clinical–pathologic cohort studies of aging and dementia in the United States, the Religious Order Study and the Memory and Aging Project, we evaluated the association of the CETP I405V polymorphism (rs5882) with cognitive decline and risk of incident AD in more than 1300 participants of European ancestry. Our results suggest that the CETP I405V polymorphism was associated with a faster rather than a slower rate of decline in cognition over time, and an increased risk of incident AD. This finding is consistent with data showing that the CETP I405V is associated with increased neuritic plaque density at autopsy.

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