APOE and cortical superficial siderosis in CAA Academic Article uri icon

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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.

authors

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

publication date

  • July 23, 2019