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Genetic association between the APOE*4 allele and Lewy bodies in Alzheimer disease

From the Departments of Psychiatry and Behavioral Sciences (Drs. Tsuang and Leverenz), Neurology (Dr. Leverenz), and Epidemiology (Dr. Tsuang), School of Public Health, University of Washington, Seattle; Departments of Neurology (Drs. Lopez and DeKosky) and Pathology (Neuropathology) (Dr. Hamilton), School of Medicine, and Department of Human Genetics (Drs. Kamboh and Luedecking-Zimmer), Graduate School of Public Health, University of Pittsburgh, PA; and Department of Neurology (Dr. Wilson), School of Medicine, Johns Hopkins University, Baltimore, MD.

Address correspondence and reprint requests to Dr. D.W. Tsuang, VAPSHCS (S-116), 1660 S. Columbian Way, Seattle, WA 98108; e-mail: dwt1{at}u.washington.edu

Objective: To explore the association between APOE*4 and pathologically confirmed cases of the Lewy body (LB) variant of Alzheimer disease (AD).

Methods: With use of -synuclein (AS) immunohistochemistry, LBs were detected in 74 of 131 (56.5%) of the AD + LB cases; the remaining 57 cases (43.5%) did not have LBs.

Results: There were no differences in gender or age between Caucasian subjects with AD + LB or AD alone or control subjects. The APOE*4 allele frequency was highest in the AD + LB group (47.3%; 95% CI = 37.8 to 57.0%), intermediate in the AD-alone group (35.1%; 95% CI = 25.3 to 46.3%), and lowest in the control group (14.2%; 95% CI = 10.5 to 18.9%). With use of logistic regression analysis, the odds of having AD + LB vs AD alone were 2.1-fold (95% CI = 1.0 to 4.5, p = 0.055) greater in persons with an APOE*4 allele than in those without an APOE*4 allele.

Conclusion: The APOE*4 allele is associated with the presence of concomitant Lewy bodies in Alzheimer disease.

Supported in part by research grant AG05133 from the National Institute on Aging and the Alzheimer’s Disease Research Center at the University of Pittsburgh (R.L.H., S.T.D., O.L.L., E.K.L.-Z., M.I.K.), by National Institute of Neurological Disorders and Stroke grant RO1 NS48595 (R.L.H., D.W.T., J.B.L.), by National Institute on Aging grant AG13672 (M.I.K., E.K.L.-Z.), and the Veteran Affairs VISN-20 Mental Illness Research, Education, and Clinical Center and Parkinson’s Disease Research, Education, and Clinical Center (D.W.T., J.B.L.).

Received August 1, 2004. Accepted in final form October 11, 2004.

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