María Carmona-Iragui1, Mircea Balasa2, Bessy Benejam3, Daniel Alcolea4, Susana Fernández3, Laura Videla3, Isabel Sala4, María Belén Sánchez-Saudinós4, Estrella Morenas-Rodriguez4, Roser Ribosa-Nogué4, Ignacio Illán-Gala4, Sofía Gonzalez-Ortiz5, Jordi Clarimón4, Frederick Schmitt6, David K Powell6, Beatriz Bosch7, Albert Lladó7, Michael S Rafii8, Elizabeth Head6, José Luis Molinuevo9, Rafael Blesa4, Sebastián Videla10, Alberto Lleó4, Raquel Sánchez-Valle7, Juan Fortea11. 1. Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Barcelona Down Medical Center, Fundació Catalana de Síndrome de Down, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, CIBERNED, Madrid, Spain; Global Brain Health Institute, Trinity College Dublin, College Green, Dublin, Ireland. 2. Global Brain Health Institute, Trinity College Dublin, College Green, Dublin, Ireland; Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Department, Hospital Clínic, Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain. 3. Barcelona Down Medical Center, Fundació Catalana de Síndrome de Down, Barcelona, Spain. 4. Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, CIBERNED, Madrid, Spain. 5. Department of Radiology, Hospital del Mar, Universitat Autònoma de Barcelona, Barcelona, Spain. 6. Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA. 7. Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Department, Hospital Clínic, Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain. 8. Adult Down Syndrome Clinic, Department of Neuroscience, University of California, San Diego, CA, USA; Alzheimer's Therapeutic Research Institute, University of Southern California, San Diego, CA, USA. 9. Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Department, Hospital Clínic, Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain; BarcelonaBeta Brain Research Center, Fundació Pasqual Maragall, Universitat Pompeu Fabra, Barcelona, Spain. 10. Barcelona Down Medical Center, Fundació Catalana de Síndrome de Down, Barcelona, Spain; Faculty of Health and Life Sciences, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain. 11. Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Barcelona Down Medical Center, Fundació Catalana de Síndrome de Down, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, CIBERNED, Madrid, Spain. Electronic address: jfortea@santpau.cat.
Abstract
INTRODUCTION: We aimed to investigate if cerebral amyloid angiopathy (CAA) is more frequent in genetically determined than in sporadic early-onset forms of Alzheimer's disease (AD) (early-onset AD [EOAD]). METHODS: Neuroimaging features of CAA, apolipoprotein (APOE), and cerebrospinal fluid amyloid β (Aβ) 40 levels were studied in subjects with Down syndrome (DS, n = 117), autosomal-dominant AD (ADAD, n = 29), sporadic EOAD (n = 42), and healthy controls (n = 68). RESULTS: CAA was present in 31%, 38%, and 12% of cognitively impaired DS, symptomatic ADAD, and sporadic EOAD subjects and in 13% and 4% of cognitively unimpaired DS individuals and healthy controls, respectively. APOE ε4 genotype was borderline significantly associated with CAA in sporadic EOAD (P = .06) but not with DS or ADAD. There were no differences in Aβ040 levels between groups or between subjects with and without CAA. DISCUSSION: CAA is more frequently found in genetically determined AD than in sporadic EOAD. Cerebrospinal fluid Aβ40 levels are not a useful biomarker for CAA in AD.
INTRODUCTION: We aimed to investigate if cerebral amyloid angiopathy (CAA) is more frequent in genetically determined than in sporadic early-onset forms of Alzheimer's disease (AD) (early-onset AD [EOAD]). METHODS: Neuroimaging features of CAA, apolipoprotein (APOE), and cerebrospinal fluid amyloid β (Aβ) 40 levels were studied in subjects with Down syndrome (DS, n = 117), autosomal-dominant AD (ADAD, n = 29), sporadic EOAD (n = 42), and healthy controls (n = 68). RESULTS: CAA was present in 31%, 38%, and 12% of cognitively impaired DS, symptomatic ADAD, and sporadic EOAD subjects and in 13% and 4% of cognitively unimpaired DS individuals and healthy controls, respectively. APOE ε4 genotype was borderline significantly associated with CAA in sporadic EOAD (P = .06) but not with DS or ADAD. There were no differences in Aβ040 levels between groups or between subjects with and without CAA. DISCUSSION: CAA is more frequently found in genetically determined AD than in sporadic EOAD. Cerebrospinal fluid Aβ40 levels are not a useful biomarker for CAA in AD.
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