Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/21696
Title: APOE and cortical superficial siderosis in CAA: Meta-analysis and potential mechanisms
Authors: Charidimou, A;Zonneveld, HI;Shams, S;Kantarci, K;Shoamanesh, A;Hilal, S;Yates, Paul A;Boulouis, G;Na, HK;Pasi, M;Biffi, A;Chai, YL;Chong, JR;Wahlund, LO;Jack, C;Chen, C;Gurol, ME;Goldstein, JN;Na, DL;Barkhof, F;Seo, SW;Rosand, J;Greenberg, SM;Viswanathan, A
Affiliation: Austin Health, Heidelberg, Victoria, Australia
Department of Nuclear Medicine and Centre for PET,The University of Melbourne, Parkville, Australia
Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
Department of Radiology, Mayo Clinic, Rochester, MN
Department of Medicine (Neurology),McMaster University and Population Health Research Institute, Hamilton, Canada
Memory, Aging and Cognition Center, National University Health System, Singapore
Department of Pharmacology, National University of Singapore
Hemorrhagic Stroke Research Program, Department of Neurology, Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston
Alzheimer Center and the Neuroscience Campus Amsterdam and Departments of Radiology and Nuclear Medicine, VU University Medical Center, the Netherlands
|Department of Neuroradiology,Université Paris-Descartes, INSERM U894, CH Sainte-Anne, Paris, France|Department of Neurology and Neuroscience Center, Samsung Medical Center, Seoul, Republic of Korea|UCL Institutes of Neurology and Healthcare Engineering,London, UK|and Center for Genomic Medicine and Division of Neurocritical Care and Emergency Neurology,Massachusetts General Hospital, Harvard Medical School, Boston
Issue Date: 23-Jul-2019
EDate: 2019-06-26
Citation: Neurology 2019; 93(4): e358-e371
Abstract: 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.
URI: http://ahro.austin.org.au/austinjspui/handle/1/21696
DOI: 10.1212/WNL.0000000000007818
PubMed URL: https://www.ncbi.nlm.nih.gov/pubmed/31243071
Type: Journal Article
Type of Clinical Study or Trial: Meta-Analysis
Appears in Collections:Journal articles

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