Andreas Charidimou1, Hazel I Zonneveld2, Sara Shams2, Kejal Kantarci2, Ashkan Shoamanesh2, Saima Hilal2, Paul A Yates2, Gregoire Boulouis2, Han Kyu Na2, Marco Pasi2, Allesandro Biffi2, Yuek Ling Chai2, Joyce Ruifen Chong2, Lars-Olof Wahlund2, Jack R Clifford2, Christopher Chen2, M Edip Gurol2, Joshua N Goldstein2, Duk L Na2, Frederik Barkhof2, Sang Won Seo2, Jonathan Rosand2, Steven M Greenberg2, Anand Viswanathan2. 1. From the Hemorrhagic Stroke Research Program, Department of Neurology (A.C., M.P., A.B., M.E.G., J.N.G., J.R., S.M.G., A.V.), Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston; Alzheimer Center and the Neuroscience Campus Amsterdam and Departments of Radiology and Nuclear Medicine (H.I.Z., F.B.), VU University Medical Center, the Netherlands; Karolinska Institutet (S.S., L.-O.W.), Karolinska University Hospital, Stockholm, Sweden; Department of Radiology (K.K., J.R.C.), Mayo Clinic, Rochester, MN; Department of Medicine (Neurology) (A.S.), McMaster University and Population Health Research Institute, Hamilton, Canada; Memory, Aging and Cognition Center (S.H., Y.L.C., J.R.C., C.C.), National University Health System, Singapore; Department of Pharmacology (S.H., Y.L.C., J.R.C., C.C.), National University of Singapore; Department of Nuclear Medicine and Centre for PET (P.A.Y.), The University of Melbourne, Parkville, Australia; Department of Neuroradiology (G.B.), Université Paris-Descartes, INSERM U894, CH Sainte-Anne, Paris, France; Department of Neurology and Neuroscience Center (H.K.N., D.L.N., S.W.S.), Samsung Medical Center, Seoul, Republic of Korea; UCL Institutes of Neurology and Healthcare Engineering (F.B.), London, UK; and Center for Genomic Medicine (J.R.) and Division of Neurocritical Care and Emergency Neurology (J.R.), Massachusetts General Hospital, Harvard Medical School, Boston. andreas.charidimou.09@ucl.ac.uk. 2. From the Hemorrhagic Stroke Research Program, Department of Neurology (A.C., M.P., A.B., M.E.G., J.N.G., J.R., S.M.G., A.V.), Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston; Alzheimer Center and the Neuroscience Campus Amsterdam and Departments of Radiology and Nuclear Medicine (H.I.Z., F.B.), VU University Medical Center, the Netherlands; Karolinska Institutet (S.S., L.-O.W.), Karolinska University Hospital, Stockholm, Sweden; Department of Radiology (K.K., J.R.C.), Mayo Clinic, Rochester, MN; Department of Medicine (Neurology) (A.S.), McMaster University and Population Health Research Institute, Hamilton, Canada; Memory, Aging and Cognition Center (S.H., Y.L.C., J.R.C., C.C.), National University Health System, Singapore; Department of Pharmacology (S.H., Y.L.C., J.R.C., C.C.), National University of Singapore; Department of Nuclear Medicine and Centre for PET (P.A.Y.), The University of Melbourne, Parkville, Australia; Department of Neuroradiology (G.B.), Université Paris-Descartes, INSERM U894, CH Sainte-Anne, Paris, France; Department of Neurology and Neuroscience Center (H.K.N., D.L.N., S.W.S.), Samsung Medical Center, Seoul, Republic of Korea; UCL Institutes of Neurology and Healthcare Engineering (F.B.), London, UK; and Center for Genomic Medicine (J.R.) and Division of Neurocritical Care and Emergency Neurology (J.R.), Massachusetts General Hospital, Harvard Medical School, Boston.
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.
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: S M Greenberg; J P Vonsattel; A Z Segal; R I Chiu; A E Clatworthy; A Liao; B T Hyman; G W Rebeck Journal: Neurology Date: 1998-04 Impact factor: 9.910
Authors: Sara Shams; Juha Martola; Andreas Charidimou; Lena Cavallin; Tobias Granberg; Mana Shams; Yngve Forslin; Peter Aspelin; Maria Kristoffersen-Wiberg; Lars-Olof Wahlund Journal: Neurology Date: 2016-08-17 Impact factor: 9.910
Authors: Eva Martínez-Lizana; María Carmona-Iragui; Daniel Alcolea; Manuel Gómez-Choco; Eduard Vilaplana; María B Sánchez-Saudinós; Jordi Clarimón; Mar Hernández-Guillamon; Josep Munuera; Ellen Gelpi; Beatriz Gómez-Anson; Manel de Juan-Delago; Raquel Delgado-Mederos; Joan Montaner; Angel Ois; Sergi Amaro; Rafael Blesa; Joan Martí-Fàbregas; Alberto Lleó; Juan Fortea Journal: J Cereb Blood Flow Metab Date: 2015-03-04 Impact factor: 6.200
Authors: Andreas Charidimou; Gregoire Boulouis; Li Xiong; Michel J Jessel; Duangnapa Roongpiboonsopit; Alison Ayres; Kristin M Schwab; Jonathan Rosand; M Edip Gurol; Steven M Greenberg; Anand Viswanathan Journal: Neurology Date: 2017-03-29 Impact factor: 9.910
Authors: S S Maxwell; C A Jackson; L Paternoster; C Cordonnier; V Thijs; R Al-Shahi Salman; C L M Sudlow Journal: Neurology Date: 2011-06-29 Impact factor: 9.910
Authors: Seth Love; Katy Chalmers; Paul Ince; Margaret Esiri; Johannes Attems; Kurt Jellinger; Masahito Yamada; Mark McCarron; Thais Minett; Fiona Matthews; Steven Greenberg; David Mann; Patrick Gavin Kehoe Journal: Am J Neurodegener Dis Date: 2014-03-28
Authors: Andreas Charidimou; Gregoire Boulouis; Duangnapa Roongpiboonsopit; Eitan Auriel; Marco Pasi; Kellen Haley; Ellis S van Etten; Sergi Martinez-Ramirez; Alison Ayres; Anastasia Vashkevich; Kristin M Schwab; Joshua N Goldstein; Jonathan Rosand; Anand Viswanathan; Steven M Greenberg; M Edip Gurol Journal: Neurology Date: 2017-10-25 Impact factor: 11.800
Authors: Isabel Charlotte Hostettler; David Seiffge; Andrew Wong; Gareth Ambler; Duncan Wilson; Clare Shakeshaft; Gargi Banerjee; Nikhil Sharma; Hans Rolf Jäger; Hannah Cohen; Tarek A Yousry; Rustam Al-Shahi Salman; Gregory Y H Lip; Martin M Brown; Keith Muir; Henry Houlden; David J Werring Journal: Neurology Date: 2022-07-08 Impact factor: 11.800
Authors: Rita Guerreiro; Elizabeth Gibbons; Miguel Tábuas-Pereira; Celia Kun-Rodrigues; Gustavo C Santo; Jose Bras Journal: Neurobiol Dis Date: 2020-05-19 Impact factor: 5.996
Authors: Patryk Kubiszewski; Lansing Sugita; Christina Kourkoulis; Zora DiPucchio; Kristin Schwab; Christopher D Anderson; M Edip Gurol; Steven M Greenberg; Anand Viswanathan; Jonathan Rosand; Alessandro Biffi Journal: JAMA Neurol Date: 2020-08-31 Impact factor: 18.302
Authors: Qi Li; Maria Clara Zanon Zotin; Andrew D Warren; Yuan Ma; Edip Gurol; Joshua N Goldstein; Steven M Greenberg; Andreas Charidimou; Nicolas Raposo; Anand Viswanathan Journal: Neurology Date: 2020-10-21 Impact factor: 9.910