2026-04-13T02:40:13Zhttps://recercat.cat/oai/request
oai:recercat.cat:2072/4785062025-10-13T12:17:21Zcom_2072_98col_2072_378192
RECERCAT author Montoliu-Gaya, Laia author Alcolea, Daniel author Ashton, Nicholas J author Pegueroles, Jordi author Levin, Johannes author Bosch, Beatriz author Lantero-Rodriguez, Juan author Carmona Iragui, María author Wagemann, Olivia author Balasa, Mircea author Kac, Przemysław R. author Barroeta, Isabel author Llado Plarrumani, Albert author Scheeren Brum, Wagner author Videla Toro, Laura author Gonzalez-Ortiz, Fernando author Benejam, Bessy author Arranz Martínez, Javier author Karikari, Thomas K. author Nübling, Georg author Bejanin, Alexandre author Benedet, Andréa Lessa author Blesa, Rafael author Lleó, Alberto author Blennow, Kaj author Sanchez-Valle, Raquel author Zetterberg, Henrik author Fortea, Juan author Universitat Autònoma de Barcelona 2023 The diagnosis of symptomatic Alzheimer's disease is a clinical challenge in adults with Down syndrome. Blood biomarkers would be of particular clinical importance in this population. The astrocytic Glial Fibrillary Acidic Protein (GFAP) is a marker of astrogliosis associated with amyloid pathology, but its longitudinal changes, association with other biomarkers and cognitive performance have not been studied in individuals with Down syndrome. We performed a three-centre study of adults with Down syndrome, autosomal dominant Alzheimer's disease and euploid individuals enrolled in Hospital Sant Pau, Barcelona (Spain), Hospital Clinic, Barcelona (Spain) and Ludwig-Maximilians-Universität, Munich (Germany). Cerebrospinal fluid (CSF) and plasma GFAP concentrations were quantified using Simoa. A subset of participants had PET F-fluorodeoxyglucose, amyloid tracers and MRI measurements. This study included 997 individuals, 585 participants with Down syndrome, 61 Familial Alzheimer's disease mutation carriers and 351 euploid individuals along the Alzheimer's disease continuum, recruited between November 2008 and May 2022. Participants with Down syndrome were clinically classified at baseline as asymptomatic, prodromal Alzheimer's disease and Alzheimer's disease dementia. Plasma GFAP levels were significantly increased in prodromal and Alzheimer's disease dementia compared to asymptomatic individuals and increased in parallel to CSF Aβ changes, ten years prior to amyloid PET positivity. Plasma GFAP presented the highest diagnostic performance to discriminate symptomatic from asymptomatic groups (AUC = 0.93, 95% CI 0.9-0.95) and its concentrations were significantly higher in progressors vs non-progressors (p < 0.001), showing an increase of 19.8% (11.8-33.0) per year in participants with dementia. Finally, plasma GFAP levels were highly correlated with cortical thinning and brain amyloid pathology. Our findings support the utility of plasma GFAP as a biomarker of Alzheimer's disease in adults with Down syndrome, with possible applications in clinical practice and clinical trials. AC Immune, La Caixa Foundation, Instituto de Salud Carlos III, National Institute on Aging, Wellcome Trust, Jérôme Lejeune Foundation, Medical Research Council, Alzheimer's Association, National Institute for Health Research, EU Joint Programme-Neurodegenerative Disease Research, Alzheimer's Society, Deutsche Forschungsgemeinschaft, Stiftung für die Erforschung von Verhaltens, Fundación Tatiana Pérez de Guzmán el Bueno & European Union's Horizon 2020 und Umwelteinflüssen auf die menschliche Gesundheit. open access Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades. https://creativecommons.org/licenses/by-nc-nd/4.0/ Alzheimer's disease Down syndrome GFAP Plasma Plasma and cerebrospinal fluid glial fibrillary acidic protein levels in adults with Down syndrome : a longitudinal cohort study Article