title: Interrelationship of superficial siderosis and microbleeds in cerebral amyloid angiopathy.
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.affiliation: From the Hemorrhagic Stroke Research Program, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: Ashkan
authors.initials: A
authors.lastname: Shoamanesh
authors.affiliation: From the Hemorrhagic Stroke Research Program, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: Sergi
authors.initials: S
authors.lastname: Martinez-Ramirez
authors.affiliation: From the Hemorrhagic Stroke Research Program, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: Jamary
authors.initials: J
authors.lastname: Oliveira-Filho
authors.affiliation: From the Hemorrhagic Stroke Research Program, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: Yael
authors.initials: Y
authors.lastname: Reijmer
authors.affiliation: From the Hemorrhagic Stroke Research Program, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: Guido J
authors.initials: GJ
authors.lastname: Falcone
authors.affiliation: From the Hemorrhagic Stroke Research Program, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: Alison
authors.initials: A
authors.lastname: Ayres
authors.affiliation: From the Hemorrhagic Stroke Research Program, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: Kristin
authors.initials: K
authors.lastname: Schwab
authors.affiliation: From the Hemorrhagic Stroke Research Program, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: Joshua N
authors.initials: JN
authors.lastname: Goldstein
authors.affiliation: From the Hemorrhagic Stroke Research Program, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Rosand
authors.affiliation: From the Hemorrhagic Stroke Research Program, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: M Edip
authors.initials: ME
authors.lastname: Gurol
authors.affiliation: From the Hemorrhagic Stroke Research Program, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: Anand
authors.initials: A
authors.lastname: Viswanathan
authors.affiliation: From the Hemorrhagic Stroke Research Program, Massachusetts General Hospital, Harvard Medical School, Boston, MA. sgreenberg@mgh.harvard.edu.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Greenberg
mesh_terms: D000368:Aged; D001057:Apolipoproteins E / Q000235:genetics; D016657:Cerebral Amyloid Angiopathy / Q000150:complications* / Q000235:genetics; D002540:Cerebral Cortex / Q000473:pathology; D002543:Cerebral Hemorrhage / Q000150:complications* / Q000209:etiology* / Q000235:genetics; D016009:Chi-Square Distribution; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D012806:Siderosis / Q000150:complications* / Q000209:etiology* / Q000235:genetics
chemical_list: D001057:Apolipoproteins E