APOE ε4 and risk for Alzheimer's disease: do regionally distributed white matter hyperintensities play a role?

Adam M Brickman; Nicole Schupf; Jennifer J Manly; Yaakov Stern; José A Luchsinger; Frank A Provenzano; Atul Narkhede; Qolamreza Razlighi; Lyndsey Collins-Praino; Sylvaine Artero; Tasnime N Akbaraly; Karen Ritchie; Richard Mayeux; Florence Portet

doi:10.1016/j.jalz.2014.07.155

APOE ε4 and risk for Alzheimer's disease: do regionally distributed white matter hyperintensities play a role?

Alzheimers Dement. 2014 Nov;10(6):619-29. doi: 10.1016/j.jalz.2014.07.155. Epub 2014 Oct 7.

Authors

Affiliations

¹ Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA; G.H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA; Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA. Electronic address: amb2139@columbia.edu.
² Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA; G.H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA; Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.
³ Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA; G.H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA; Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
⁴ Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA; G.H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA; Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA; Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
⁵ Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA; Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
⁶ Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
⁷ Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA; Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
⁸ Inserm, 1061 Neuropsychiatry, La Colombière Hospital, Montpellier, France; Faculty of Medicine University of Montpellier 1, Montpellier, France.
⁹ Inserm, 1061 Neuropsychiatry, La Colombière Hospital, Montpellier, France; Faculty of Medicine University of Montpellier 1, Montpellier, France; Department of Epidemiology and Public Health, Faculty of Medicine, Imperial College, University College London, London, UK.
¹⁰ Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA; G.H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA; Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA; Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA; Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY, USA. Electronic address: rpm2@cumc.columbia.edu.

Abstract

Background: We previously demonstrated that parietal lobe white matter hyperintensities (WMH) increase the risk for Alzheimer's disease (AD). Here, we examined whether individuals with apolipoprotein E gene (APOE ε4) have increased parietal WMH volume.

Methods: Participants were from the Washington Heights-Inwood Columbia Aging Project (WHICAP; n = 694, 47 with dementia) in northern Manhattan and the Etude Santé Psychologique Prévalence Risques et Traitement study (ESPRIT; n = 539, 8 with dementia) in Montpellier. The association between regional WMH and APOE ε4 was examined separately in each group and then in a combined analysis.

Results: In WHICAP, ε4 carriers had higher WMH volume particularly in parietal and occipital lobes. In ESPRIT, ε4 carriers had elevated WMH particularly in parietal and temporal lobes. In the combined analysis, ε4 carriers had higher WMH in parietal and occipital lobes. Increased WMH volume was associated with increased frequency of dementia irrespective of APOE ε4 status; those with the ε4 were more likely to have dementia if they also had increased parietal WMH.

Conclusions: APOE ε4 is associated with increased parietal lobe WMH.

Keywords: APOE; Alzheimer's disease; White matter hyperintensities.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aged, 80 and over
Alzheimer Disease / genetics*
Alzheimer Disease / pathology*
Analysis of Variance
Apolipoprotein E4 / genetics*
Female
Genotype
Humans
Image Processing, Computer-Assisted
Linear Models
Longitudinal Studies
Magnetic Resonance Imaging
Male
Neurologic Examination
Neuropsychological Tests
Parietal Lobe / pathology*
Retrospective Studies
White Matter / pathology*

Substances

Apolipoprotein E4

Abstract

Publication types

MeSH terms

Substances

Grants and funding