Genetics of cerebral amyloid angiopathy: systematic review and meta-analysis

Background and purpose Cerebral amyloid angiopathy (CAA) is common in the ageing brain and is associated with dementia and lobar intracerebral haemorrhage. We systematically reviewed genetic associations with CAA to better understand its pathogenesis. Methods We comprehensively sought and critically appraised published studies of associations between any genetic polymorphism and histopathologically confirmed CAA. We assessed the effects of genotype by calculating study specific and pooled odds ratios (ORs) in meta-analyses, and assessed small study bias. Results 58 studies (6855 participants) investigated apolipoprotein E (APOE) genotype and sporadic CAA. Meta-analysis of 24 (3520 participants) of these showed an association of APOE ɛ4 with CAA (ɛ4 present vs absent, pooled OR 2.7, 95% CI 2.3 to 3.1, p Conclusions There is convincing evidence for a dose dependent association between APOE ɛ4 and sporadic CAA. Further work is needed to better understand the mechanism of this association and to further investigate other genetic associations with CAA.