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The effect of APOE on dementia is not through atherosclerosis: The Rotterdam Study

From the Department of Epidemiology & Biostatistics (Drs. Slooter, Ott, Bots, Witteman, Hofman, Breteler, and van Duijn), Erasmus University Medical School, Rotterdam, the Netherlands; the University Department of Neurology (Dr. Slooter) and Julius Center for Patient Oriented Research (Dr. Bots), Utrecht University, the Netherlands; and Neurogenetics Laboratory, Flanders Interuniversity Institute for Biotechnology (VIB), Born-Bunge Foundation (BBS), Department of Biochemistry (Drs. Cruts and Van Broeckhoven), University of Antwerp (UIA), Antwerpen, Belgium.

Address correspondence and reprint requests to Dr. A.J.C. Slooter, Department of Epidemiology & Biostatistics, Erasmus University Medical School, PO Box 1738, 3000 DR Rotterdam, the Netherlands.

The APOE genotype is involved in atherosclerosis, and atherosclerosis increases the risk of dementia, in particular among carriers of the APOE-4 allele. We studied, in a population-based setting (244 dementia cases; 1,002 nondemented controls), whether APOE is associated with dementia through atherosclerosis. As neither adjusting nor stratification for atherosclerosis altered the association of APOE with dementia, our study suggests that atherosclerosis is not an intermediate factor.

Key words: APOE—Dementia—Atherosclerosis—The Rotterdam Study.

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