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APOE associations with severe CAA-associated vasculopathic changes: collaborative meta-analysis.

ABSTRACT: Cerebral amyloid angiopathy (CAA) is associated with lobar intracerebral haemorrhage (ICH). While only the ?4 allele of the apolipoprotein E (APOE) gene is associated with the presence of CAA, both APOE-?4 and ?2 are associated with lobar ICH. The generally accepted explanation is that APOE-?4 promotes vascular amyloid deposition, while APOE-?2 promotes progression to severe CAA with associated vasculopathic changes that cause vessel rupture and ICH. We assessed the evidence for these allele-specific effects.We systematically identified published studies with data on APOE genotype and histopathological assessment of postmortem brains for CAA severity. We obtained unpublished data from these for meta-analyses of the effects of ?4-containing (?4+) and ?2-containing (?2+) genotypes on progression to severe CAA.Of six eligible studies (543 eligible participants), data were available from 5 (497 participants, 353 with CAA). Meta-analyses showed a possible association of ?4+ genotypes with severe CAA (?4+ vs ?4-: severe vs mild/moderate CAA, OR 2.5, 95% CI 1.4 to 4.5, p=0.002; severe vs moderate CAA, OR 1.7, 95% CI 0.9 to 3.1, p=0.11). For ?2+ versus ?2- genotypes, there was no significant association, but the very small number of participants with ?2+ genotypes (22) precluded reliable estimates.We found a possible association of severe CAA with APOE-?4 but not APOE-?2. However, our findings do not exclude a biologically meaningful association between APOE-?2 and severe CAA. Further work is needed to elucidate fully the allele-specific associations of APOE with CAA and their mechanisms.

SUBMITTER: Rannikmae K

PROVIDER: S-EPMC4018226 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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APOE associations with severe CAA-associated vasculopathic changes: collaborative meta-analysis.

Rannikmäe Kristiina K Kalaria Rajesh N RN Greenberg Steven M SM Chui Helena C HC Schmitt Frederick A FA Samarasekera Neshika N Al-Shahi Salman Rustam R Sudlow Cathie L M CL

Journal of neurology, neurosurgery, and psychiatry 20131025 3

<h4>Objectives</h4>Cerebral amyloid angiopathy (CAA) is associated with lobar intracerebral haemorrhage (ICH). While only the ε4 allele of the apolipoprotein E (APOE) gene is associated with the presence of CAA, both APOE-ε4 and ε2 are associated with lobar ICH. The generally accepted explanation is that APOE-ε4 promotes vascular amyloid deposition, while APOE-ε2 promotes progression to severe CAA with associated vasculopathic changes that cause vessel rupture and ICH. We assessed the evidence f ...[more]

PMID: 24163429

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Dataset Information

APOE associations with severe CAA-associated vasculopathic changes: collaborative meta-analysis.

Publications

APOE associations with severe CAA-associated vasculopathic changes: collaborative meta-analysis.

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