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Cholesterol and APOE genotype interact to influence Alzheimer disease progression

From the Departments of Neurology (Drs. Evans and Farlow), Medicine (Dr. Hui), and Psychiatry (Dr. Lahiri) and Regenstrief Institute for Health Care (Dr. Hui, A. Perkins), Indiana University School of Medicine, Indianapolis; and McGill Centre for Studies in Aging (Dr. Poirier), Montreal, Quebec, Canada.

Address correspondence and reprint requests to Dr. R.M. Evans, Department of Neurology, CL 299, 541 Clinical Dr., Indianapolis, IN 46202; e-mail: revans1{at}iupui.edu

In this retrospective analysis of 443 Alzheimer disease (AD) patients from a 30-week tacrine trial, change in Alzheimer’s Disease Assessment Scale score from baseline to final value was significantly associated with a total serum cholesterol/APOE genotype interaction. Disease progression in the no-APOE 4 allele/high-cholesterol subgroup was greater than in the normal-cholesterol subgroups with or without 4. Cholesterol levels and APOE genotype may interact to affect AD progression. The results are consistent with preclinical data on cholesterol’s effects in AD.

Received September 12, 2003. Accepted in final form January 15, 2004.

Drs. Farlow and Poirier have served as consultants, received honoraria, and conducted clinical trials for Parke Davis (tacrine).

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