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(Stroke. 2005;36:954.)
© 2005 American Heart Association, Inc.

Original Contributions

The Apolipoprotein E 4 Allele Increases the Odds of Chronic Cerebral Infarction Detected at Autopsy in Older Persons

J.A. Schneider, MD; J.L. Bienias, ScD; R.S. Wilson, PhD; E. Berry-Kravis, MD, PhD; D.A. Evans, MD D.A. Bennett, MD

From Rush AD Center and Rush Institute for Healthy Aging (D.A.B., R.S.W., D.A.E., J.A.S., J.L.B.), Department of Psychology (R.S.W.), Department of Neurological Sciences (D.A.B., R.S.W., D.A.E., J.A.S.), Department of Pathology (J.A.S.), Department of Internal Medicine (D.A.E., J.L.B.), Rush University Medical Center, Chicago, Ill.

Correspondence to Julie A. Schneider, MD, Rush AD Center, 600 S. Paulina St, AAC, Suite 1022F, Chicago, IL 60612. E-mail Julie_A_Schneider{at}rush.edu

Background and Purpose— Studies investigating the relation of the apolipoprotein E (apoE) 4 allele to clinical stroke and to vascular changes on magnetic resonance imaging have been conflicting. Little data are available regarding the relation of apoE 4 to cerebral infarctions documented on postmortem examination.

Methods— We studied the apoE 4 allele in 214 deceased members of the Religious Orders Study, a longitudinal clinical–pathologic study of aging and Alzheimer disease. The apoE genotype was determined using DNA from lymphocytes. Brains were removed a median of 5 hours (interquartile range, 5.5) after death. At postmortem examination, age, location, and size of macroscopic chronic cerebral infarctions were recorded from 1-cm coronal slabs after paraformaldehyde fixation. We also examined 20-µm paraffin-embedded sections of midfrontal and calcarine cortex for amyloid angiopathy on a scale of 1 to 4.

Results— Subjects included 96 males and 118 females with a mean age at death of 86 years (SD, 7). Sixty-five subjects (30.4%) had at least 1 apoE 4 allele and 76 (35.5%) exhibited cerebral infarctions. More than 74% of the subjects exhibited amyloid angiopathy with a mean score of 1.4±1.2. After controlling for age and sex, apoE 4 increased the odds of cerebral infarction by 2.3-fold (95% CI, 1.2 to 4.2). apoE 4 increased the odds of cortical 3.2-fold (95% CI, 1.3 to 7.7) and subcortical infarctions 2.3-fold (95% CI, 1.2 to 4.5). The effect was unchanged after accounting for amyloid angiopathy.

Conclusions— apoE 4 increases the odds of chronic cerebral infarction detected at autopsy in older persons.

Key Words: cerebral infarction • epidemiologic methods • genetics • pathology

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