APOE and cortical superficial siderosis in CAA: Meta-analysis and potential mechanisms

Andreas Charidimou, Hazel I. Zonneveld, Sara Shams, Kejal Kantarci, Ashkan Shoamanesh, Saima Hilal, Paul A. Yates, Gregoire Boulouis, Han Kyu Na, Marco Pasi, Allesandro Biffi, Yuek Ling Chai, Joyce Ruifen Chong, Lars Olof Wahlund, Jack R. Clifford, Christopher Chen, M. Edip Gurol, Joshua N. Goldstein, Duk L. Na, Frederik BarkhofSang Won Seo, Jonathan Rosand, Steven M. Greenberg, Anand Viswanathan

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

ObjectiveTo assess potential mechanisms of cortical superficial siderosis (cSS), a central MRI biomarker in cerebral amyloid angiopathy (CAA), we performed a collaborative meta-analysis of APOE associations with cSS presence and severity.MethodsWe pooled data from published studies reporting APOE genotype and MRI assessment of cSS in 3 distinct settings: (1) stroke clinic patients with symptomatic CAA (i.e., lobar intracerebral hemorrhage, transient focal neurologic episodes) according to the Boston criteria; (2) memory clinic patients; and (3) population-based studies. We compared cSS presence and severity (focal or disseminated vs no cSS) in participants with ϵ2+ or ϵ4+ genotype vs the ϵ3/ϵ3 genotype, by calculating study-specific and random effects pooled, unadjusted odds ratios (ORs).ResultsThirteen studies fulfilled inclusion criteria: 7 memory clinic cohorts (n = 2,587), 5 symptomatic CAA cohorts (n = 402), and 1 population-based study (n = 1,379). There was no significant overall association between APOE ϵ4+ and cSS presence or severity. When stratified by clinical setting, APOE ϵ4+ was associated with cSS in memory clinic (OR 2.10; 95% confidence interval [CI] 1.11-3.99) but not symptomatic CAA patients. The pooled OR showed significantly increased odds of having cSS for APOE ϵ2+ genotypes (OR 2.42, 95% CI 1.48-3.95) in both patient populations. This association was stronger for disseminated cSS in symptomatic CAA cohorts. In detailed subgroup analyses, APOE ϵ2/ϵ2 and APOE ϵ2/ϵ4 genotypes were most consistently and strongly associated with cSS presence and severity.ConclusionCAA-related vasculopathic changes and fragility associated with APOE ϵ2+ allele might have a biologically meaningful role in the pathophysiology and severity of cSS.

Original languageEnglish (US)
Pages (from-to)E358-E371
JournalNeurology
Volume93
Issue number4
DOIs
StatePublished - Jul 23 2019

ASJC Scopus subject areas

  • Clinical Neurology

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    Charidimou, A., Zonneveld, H. I., Shams, S., Kantarci, K., Shoamanesh, A., Hilal, S., Yates, P. A., Boulouis, G., Na, H. K., Pasi, M., Biffi, A., Chai, Y. L., Chong, J. R., Wahlund, L. O., Clifford, J. R., Chen, C., Gurol, M. E., Goldstein, J. N., Na, D. L., ... Viswanathan, A. (2019). APOE and cortical superficial siderosis in CAA: Meta-analysis and potential mechanisms. Neurology, 93(4), E358-E371. https://doi.org/10.1212/WNL.0000000000007818