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Neurology 2001;56:1696-1701
© 2001 American Academy of Neurology
Articles

Gender and age modify the association between APOE and AD-related neuropathology

E. Ghebremedhin, MD;, C. Schultz, MD;, D.R. Thal, MD;, U. Rüb, MD;, T.G. Ohm, MD;, E. Braak, PhD and H. Braak, MD

From the Department of Clinical Neuroanatomy (Drs. Ghebremedhin, Schultz, Thal, Rüb, E. Braak, and H. Braak) J.W. Goethe–University, Frankfurt, Germany; and the Department of Anatomy (Dr. Ohm), Medical Faculty Charité of the Humboldt University, Berlin, Germany.

Address correspondence and reprint requests to Dr. Estifanos Ghebremedhin, Department of Clinical Neuroanatomy, J.W. Goethe–University, Theodor-Stern-Kai 7, 60590 Frankfurt/Main, Germany; e-mail: Ghebremedhin{at}em.uni-frankfurt.de

OBJECTIVE: To assess the impact of apolipoprotein E (APOE) polymorphism on AD-related neurofibrillary tangle (NFT) formation and senile plaques (SP).

METHODS: A sample of 729 routine autopsy brains (359 men, 370 women; age range, 60 to 99 years) was investigated. All brains were classified neuropathologically according to a procedure permitting differentiation of six NFT stages and three SP stages. APOE genotyping was performed on all cases.

RESULTS: The {varepsilon}4 allele of APOE was associated not only with SP (p < 0.0001) but also with NFT formation (p < 0.0001). The effect of the {varepsilon}4 allele on NFT formation was noted at ages >=80 years (p < 0.0001) but not between ages 60 and 79 years (p = 0.12). An association between the {varepsilon}4 allele and SP for women was found at ages 60 to 79 years (p < 0.0001) but not at >=80 years of age (p = 0.063). By comparison, men showed an association in both age categories (p = 0.001 and p = 0.001).

CONCLUSION: The results confirm the association between the {varepsilon}4 allele and both types of AD-related lesions and show that this association is differentially modified by age and gender.




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