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

Abstract

OBJECTIVE:

To 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.

METHODS:

We 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).

RESULTS:

Thirteen 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.

CONCLUSION:

CAA-related vasculopathic changes and fragility associated with APOE ε2+ allele might have a biologically meaningful role in the pathophysiology and severity of cSS.

• Authors: 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 Barkhof, Sang Won Seo, Jonathan Rosand, Steven M Greenberg, Anand Viswanathan
• Journal: Neurology (Neurology) Vol. 93 Issue 4 Pg. e358-e371 (07 23 2019) ISSN: 1526-632X [Electronic] United States
• PMID: 31243071 (Publication Type: Journal Article, Meta-Analysis, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 American Academy of Neurology.

Chemical References

• Apolipoprotein E2
• Apolipoprotein E3
• Apolipoprotein E4
• Apolipoproteins E

Topics

• Apolipoprotein E2
• Apolipoprotein E3
• Apolipoprotein E4
• Apolipoproteins E (genetics)
• Brain (diagnostic imaging)
• Case-Control Studies
• Cerebral Amyloid Angiopathy (diagnostic imaging)
• Cerebral Cortex (diagnostic imaging, metabolism)
• Hemosiderosis (diagnostic imaging, genetics)
• Humans
• Magnetic Resonance Imaging
• Odds Ratio