Plasma and cerebrospinal fluid glial fibrillary acidic protein levels in adults with Down syndrome: a longitudinal cohort study
Por:
Montoliu-Gaya, L, Alcolea, D, Ashton, NJ, Pegueroles, J, Levin, J, Bosch, B, Lantero-Rodriguez, J, Carmona-Iragui, M, Wagemann, O, Balasa, M, Kac, PR, Barroeta, I, Llado, A, Brum, WS, Videla, L, Gonzalez-Ortiz, F, Benejam, B, Martinez, JJA, Karikari, TK, Nubling, G, Bejanin, A, Benedet, AL, Blesa, R, Lleo, A, Blennow, K, Sanchez-Valle, R, Zetterberg, H, Fortea, J
Publicada:
1 abr 2023
Ahead of Print:
1 mar 2023
Resumen:
Background 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) isa 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. Methods 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-Universitat, Munich (Germany). Cerebrospinal fluid (CSF) and plasma GFAP concentrations were quantified using Simoa. A subset of participants had PET 18F-fluorodeoxyglucose, amyloid tracers and MRI measurements. Findings 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 asymp-tomatic, 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 A beta 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 con-centrations 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. Interpretation 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. Copyright (c) 2023 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Filiaciones:
Montoliu-Gaya, L:
Univ Gothenburg, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Sahlgrenska Acad, Molndal, Sweden
Alcolea, D:
Univ Autonoma Barcelona, Biomed Res Inst St Pau IIB St Pau, Hosp Santa Creu & St Pau, St Pau Memory Unit,Dept Neurol, Barcelona, Spain
Ctr Biomed Invest Network Neurodegenerat Dis CIBE, Madrid, Spain
Ashton, NJ:
Univ Gothenburg, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Sahlgrenska Acad, Molndal, Sweden
Univ Gothenburg, Wallenberg Ctr Mol & Translat Med, Gothenburg, Sweden
Kings Coll London, Maurice Wohl Clin Neurosci Inst, Dept Old Age Psychiat, London, England
South London & Maudsley NHS Fdn, Mental Hlth & Biomed Res Unit Dementia, NIHR Biomed Res Ctr, London, England
Pegueroles, J:
Univ Autonoma Barcelona, Biomed Res Inst St Pau IIB St Pau, Hosp Santa Creu & St Pau, St Pau Memory Unit,Dept Neurol, Barcelona, Spain
Ctr Biomed Invest Network Neurodegenerat Dis CIBE, Madrid, Spain
Levin, J:
Ludwig Maximilians Univ Munchen, Dept Neurol, Munich, Germany
German Ctr Neurodegenerat Dis, Munich, Germany
Munich Cluster Syst Neurol SyNergy, Munich, Germany
Bosch, B:
Univ Barcelona, Hosp Clin Barcelona, Inst Neurociencies, Alzheimers Dis & Other Cognit Disorders Unit,Neur, Barcelona, Spain
Lantero-Rodriguez, J:
Univ Gothenburg, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Sahlgrenska Acad, Molndal, Sweden
Carmona-Iragui, M:
Univ Autonoma Barcelona, Biomed Res Inst St Pau IIB St Pau, Hosp Santa Creu & St Pau, St Pau Memory Unit,Dept Neurol, Barcelona, Spain
Ctr Biomed Invest Network Neurodegenerat Dis CIBE, Madrid, Spain
Fundacio Catalana Sindrome Down, Barcelona Med Ctr, Barcelona, Spain
Wagemann, O:
Ludwig Maximilians Univ Munchen, Dept Neurol, Munich, Germany
German Ctr Neurodegenerat Dis, Munich, Germany
Munich Cluster Syst Neurol SyNergy, Munich, Germany
Balasa, M:
Univ Barcelona, Hosp Clin Barcelona, Inst Neurociencies, Alzheimers Dis & Other Cognit Disorders Unit,Neur, Barcelona, Spain
Kac, PR:
Univ Gothenburg, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Sahlgrenska Acad, Molndal, Sweden
Barroeta, I:
Univ Autonoma Barcelona, Biomed Res Inst St Pau IIB St Pau, Hosp Santa Creu & St Pau, St Pau Memory Unit,Dept Neurol, Barcelona, Spain
Ctr Biomed Invest Network Neurodegenerat Dis CIBE, Madrid, Spain
Llado, A:
Univ Barcelona, Hosp Clin Barcelona, Inst Neurociencies, Alzheimers Dis & Other Cognit Disorders Unit,Neur, Barcelona, Spain
Brum, WS:
Univ Gothenburg, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Sahlgrenska Acad, Molndal, Sweden
Univ Fed Rio Grande do Sul UFRGS, Grad Program Biol Sci Biochem, Porto Alegre, RS, Brazil
Videla, L:
Univ Autonoma Barcelona, Biomed Res Inst St Pau IIB St Pau, Hosp Santa Creu & St Pau, St Pau Memory Unit,Dept Neurol, Barcelona, Spain
Ctr Biomed Invest Network Neurodegenerat Dis CIBE, Madrid, Spain
Fundacio Catalana Sindrome Down, Barcelona Med Ctr, Barcelona, Spain
Gonzalez-Ortiz, F:
Univ Gothenburg, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Sahlgrenska Acad, Molndal, Sweden
Benejam, B:
Univ Autonoma Barcelona, Biomed Res Inst St Pau IIB St Pau, Hosp Santa Creu & St Pau, St Pau Memory Unit,Dept Neurol, Barcelona, Spain
Ctr Biomed Invest Network Neurodegenerat Dis CIBE, Madrid, Spain
Fundacio Catalana Sindrome Down, Barcelona Med Ctr, Barcelona, Spain
Martinez, JJA:
Univ Autonoma Barcelona, Biomed Res Inst St Pau IIB St Pau, Hosp Santa Creu & St Pau, St Pau Memory Unit,Dept Neurol, Barcelona, Spain
Ctr Biomed Invest Network Neurodegenerat Dis CIBE, Madrid, Spain
Karikari, TK:
Univ Gothenburg, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Sahlgrenska Acad, Molndal, Sweden
Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA
Nubling, G:
Ludwig Maximilians Univ Munchen, Dept Neurol, Munich, Germany
German Ctr Neurodegenerat Dis, Munich, Germany
Munich Cluster Syst Neurol SyNergy, Munich, Germany
Bejanin, A:
Univ Autonoma Barcelona, Biomed Res Inst St Pau IIB St Pau, Hosp Santa Creu & St Pau, St Pau Memory Unit,Dept Neurol, Barcelona, Spain
Ctr Biomed Invest Network Neurodegenerat Dis CIBE, Madrid, Spain
Benedet, AL:
Univ Gothenburg, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Sahlgrenska Acad, Molndal, Sweden
Blesa, R:
Univ Autonoma Barcelona, Biomed Res Inst St Pau IIB St Pau, Hosp Santa Creu & St Pau, St Pau Memory Unit,Dept Neurol, Barcelona, Spain
Ctr Biomed Invest Network Neurodegenerat Dis CIBE, Madrid, Spain
Lleo, A:
Univ Autonoma Barcelona, Biomed Res Inst St Pau IIB St Pau, Hosp Santa Creu & St Pau, St Pau Memory Unit,Dept Neurol, Barcelona, Spain
Ctr Biomed Invest Network Neurodegenerat Dis CIBE, Madrid, Spain
Blennow, K:
Univ Gothenburg, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Sahlgrenska Acad, Molndal, Sweden
Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden
Sanchez-Valle, R:
Univ Barcelona, Hosp Clin Barcelona, Inst Neurociencies, Alzheimers Dis & Other Cognit Disorders Unit,Neur, Barcelona, Spain
Zetterberg, H:
Univ Gothenburg, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Sahlgrenska Acad, Molndal, Sweden
Univ Fed Rio Grande do Sul UFRGS, Grad Program Biol Sci Biochem, Porto Alegre, RS, Brazil
UCL, Queen Sq Inst Neurol, Dept Neurodegenerat Dis, London, England
UCL, UK Dementia Res Inst, London, England
Hong Kong Ctr Neurodegenerat Dis, Hong Kong, Peoples R China
Fortea, J:
Univ Autonoma Barcelona, Biomed Res Inst St Pau IIB St Pau, Hosp Santa Creu & St Pau, St Pau Memory Unit,Dept Neurol, Barcelona, Spain
Ctr Biomed Invest Network Neurodegenerat Dis CIBE, Madrid, Spain
Fundacio Catalana Sindrome Down, Barcelona Med Ctr, Barcelona, Spain
Green Published, gold, All Open Access, Gold, Green
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