APOE associations with severe CAA-associated vasculopathic changes: collaborative meta-analysis. Issue 3 (25th October 2013)

• Record Type: Journal Article
• Authors: Rannikmäe, Kristiina; Kalaria, Rajesh N; Greenberg, Steven M; Chui, Helena C; Schmitt, Frederick A; Samarasekera, Neshika; Al-Shahi Salman, Rustam; Sudlow, Cathie L M
• Is Part Of: Journal of neurology, neurosurgery and psychiatry. Volume 85:Issue 3(2014)
• Page Start: 300
• Page End: 305
• Publication Date: 2013-10-25
• Subjects: Amyloid -- Cerebrovascular Disease -- Apolipoproteins -- Meta-Analysis -- Systematic Reviews; Neurology -- Periodicals; Nervous system -- Surgery -- Periodicals; Psychiatry -- Periodicals; 616.8
• DOI: 10.1136/jnnp-2013-306485
• Languages: English
• ISSNs: 0022-3050

Abstract

Abstract : Objectives: 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 for these allele-specific effects. Methods: 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 We obtained unpublished data from these for meta-analyses of the effects of ε4-containing (ε4+) and ε2-containing (ε2+) genotypes on progression to severe CAA. Results: Of six eligible studies (543 eligible participants), data were available from 5 (497 participants, 353 with CAA). Meta-analyses showed a possible association of ε4+ genotypes with severe CAA (ε4+ vs ε4−: 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 ε2+ versus ε2− genotypes, there was no significant association, but the very small number of participants with ε2+ genotypes (22) precluded reliable estimates. Conclusions: We found a possible association of severe CAA with APOE-ε4 but not APOE-ε2. However, our findings do not exclude a biologically meaningful association between APOE-ε2 and severe CAA. Further work is needed to elucidate fully the allele-specific associations of APOE with CAA and their mechanisms.