Interrelationship of superficial siderosis and microbleeds in cerebral amyloid angiopathy Journal Articles uri icon

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abstract

  • OBJECTIVE: We sought to explore the mechanisms leading to cerebral amyloid angiopathy (CAA)-related cortical superficial siderosis (cSS) by examining its neuroimaging and genetic association with cerebral microbleeds (CMBs). METHODS: MRI scans of 84 subjects with probable or definite CAA participating in a longitudinal research study were graded for cSS presence and severity (focal, restricted to ≤ 3 sulci vs disseminated, ≥ 4 sulci), and CMB count. APOE ε variants were directly genotyped. We performed cross-sectional analysis comparing CMB counts and APOE ε2 and ε4 allele frequency between subjects with no, focal, or disseminated cSS. RESULTS: cSS was present in 48% (n = 40) of the population. APOE ε2 was overrepresented among participants with focal (odds ratio [OR] 7.0, 95% confidence interval [CI] 1.7-29.3, p = 0.008) and disseminated (OR 11.5, 95% CI 2.8-46.2, p = 0.001) cSS relative to individuals without cSS. CMB counts decreased with increasing severity of cSS (median: 41, 38, and 15 for no cSS, focal cSS, and disseminated cSS, respectively, p = 0.09). The highest CMB count tertile was associated with APOE ε4 (OR 3.0, 95% CI 1.4-6.6, p = 0.006) relative to the lowest tertile. CONCLUSIONS: Among individuals with advanced CAA, cSS tends to occur in individuals with relatively lower CMB counts and with a distinct pattern of APOE genotypes. These results suggest that CAA-related cSS and CMBs may arise from distinct vasculopathic mechanisms.

authors

  • Shoamanesh, Ashkan
  • Martinez-Ramirez, Sergi
  • Oliveira-Filho, Jamary
  • Reijmer, Yael
  • Falcone, Guido J
  • Ayres, Alison
  • Schwab, Kristin
  • Goldstein, Joshua N
  • Rosand, Jonathan
  • Gurol, M Edip
  • Viswanathan, Anand
  • Greenberg, Steven M

publication date

  • November 11, 2014