Interrelationship of superficial siderosis and microbleeds in cerebral amyloid angiopathy

Neurology. 2014 Nov 11;83(20):1838-43. doi: 10.1212/WNL.0000000000000984. Epub 2014 Oct 15.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Apolipoproteins E / genetics
  • Cerebral Amyloid Angiopathy / complications*
  • Cerebral Amyloid Angiopathy / genetics
  • Cerebral Cortex / pathology
  • Cerebral Hemorrhage / complications*
  • Cerebral Hemorrhage / etiology*
  • Cerebral Hemorrhage / genetics
  • Chi-Square Distribution
  • Cohort Studies
  • Cross-Sectional Studies
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Siderosis / complications*
  • Siderosis / etiology*
  • Siderosis / genetics


  • Apolipoproteins E