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APOE Genotype and MRI Markers of Small Vessel Disease

Among ischemic stroke survivors, APOE 2 carriers had a higher rate of white matter hyperintensities, but not microbleeds, than noncarriers.

Cerebral amyloid angiopathy (CAA) is a major cause of lobar intracerebral hemorrhage in elders and is associated with a high prevalence of markers of small-vessel disease, including white matter hyperintensities (WMH) and cerebral microbleeds. The apolipoprotein E (APOE) 2 and 4 alleles have been associated with CAA-related lobar intracerebral hemorrhage. In the current study, the authors sought to define the associations between these MRI markers and APOE genotype in a cohort of 342 patients with ischemic stroke or TIA who were recruited from an ongoing prospective cohort study.

The researchers semiquantitatively assessed the amount of WMH and recorded the number of microbleeds in each patient. The number of bleeds was highly correlated with extent of WMH. APOE genotype was not associated with the presence or number of microbleeds. In contrast, presence of WMH was independently associated with APOE 2 (adjusted odds ratio for having the 2 allele, 2.85).

Comment: These results, obtained in ischemic stroke survivors, could suggest that APOE 2 plays a role in the pathogenesis of small-vessel disease. However, this study raises several questions that should spark further investigation. First, previous population-based studies have demonstrated an association between WMH and APOE 4, which was not observed in this cohort. Second, if there is a pathophysiologic link between APOE 2 and WMH, does stroke subtype play a role in this observed association? Third, it is possible that a subgroup of these ischemic stroke patients also had cerebral amyloid angiopathy (26% had microbleeds), which would render the interpretation more complicated. Studies with larger, more precisely defined cohorts should help resolve these questions.

— Anand Viswanathan, MD, PhD

Dr. Viswanathan is Instructor in Neurology, Stroke Service and Memory Disorders Unit, Massachusetts General Hospital and Harvard Medical School, Boston.

Published in Journal Watch Neurology June 5, 2007

Citation(s):

Lemmens R et al. Association of apolipoprotein E 2 with white matter disease but not with microbleeds. Stroke 2007 Apr; 38:1185-8.

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