Plasma glial fibrillary acidic protein and neurofilament light chain for the diagnostic and prognostic evaluation of frontotemporal dementia

Translational Neurodegeneration

Laia Muñoz¹  Rafael Blesa²  Jordi Pegueroles²  Victor Montal²  Ignacio Illán-Gala³  Miren Altuna³  Isabel Barroeta³  Miguel Santos-Santos³  Jordi Clarimón³  Andrea Subirana³  Teresa Estellés³  Isabel Sala³  Olivia Belbin³  Maria Belén Sánchez-Saudinós³  Javier Arranz³  Daniel Alcolea⁴  Nuole Zhu⁴  Alberto Lleó⁴  Maria Carmona-Iragui⁵  Juan Fortea⁵  Laura Videla⁵ 

[1] Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas (CIBERNED), 28031, Madrid, Spain;Sant Pau Memory Unit, Department of Neurology, Institut d’Investigacions Biomèdiques Sant Pau – Hospital de Sant Pau, Universitat Autònoma de Barcelona, 08041, Barcelona, Spain;Sant Pau Memory Unit, Department of Neurology, Institut d’Investigacions Biomèdiques Sant Pau – Hospital de Sant Pau, Universitat Autònoma de Barcelona, 08041, Barcelona, Spain;Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas (CIBERNED), 28031, Madrid, Spain;Sant Pau Memory Unit, Department of Neurology, Institut d’Investigacions Biomèdiques Sant Pau – Hospital de Sant Pau, Universitat Autònoma de Barcelona, 08041, Barcelona, Spain;Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas (CIBERNED), 28031, Madrid, Spain;Autonomous University of Barcelona, 08913, Barcelona, Spain;Sant Pau Memory Unit, Department of Neurology, Institut d’Investigacions Biomèdiques Sant Pau – Hospital de Sant Pau, Universitat Autònoma de Barcelona, 08041, Barcelona, Spain;Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas (CIBERNED), 28031, Madrid, Spain;Fundación Catalana Síndrome de Down, Centre Mèdic Down, 08029, Barcelona, Spain;

关键词: Glial fibrillary acidic protein;    Neurofilament;    Frontotemporal dementia;    Plasma biomarkers;   

DOI  :  10.1186/s40035-021-00275-w

来源: Springer

【 摘 要 】

BackgroundAstrocytes play an essential role in neuroinflammation and are involved in the pathogenesis of neurodenegerative diseases. Studies of glial fibrillary acidic protein (GFAP), an astrocytic damage marker, may help advance our understanding of different neurodegenerative diseases. In this study, we investigated the diagnostic performance of plasma GFAP (pGFAP), plasma neurofilament light chain (pNfL) and their combination for frontotemporal dementia (FTD) and Alzheimer’s disease (AD) and their clinical utility in predicting disease progression.MethodspGFAP and pNfL concentrations were measured in 72 FTD, 56 AD and 83 cognitively normal (CN) participants using the Single Molecule Array technology. Of the 211 participants, 199 underwent cerebrospinal (CSF) analysis and 122 had magnetic resonance imaging. We compared cross-sectional biomarker levels between groups, studied their diagnostic performance and assessed correlation between CSF biomarkers, cognitive performance and cortical thickness. The prognostic performance was investigated, analyzing cognitive decline  through group comparisons by tertile.ResultsUnlike pNfL, which was increased similarly in both clinical groups, pGFAP was increased in FTD but lower than in AD (all P < 0.01). Combination of both plasma markers improved the diagnostic performance to discriminate FTD from AD (area under the curve [AUC]: combination 0.78; pGFAP 0.7; pNfL 0.61, all P < 0.05). In FTD, pGFAP correlated with cognition, CSF and plasma NfL, and cortical thickness (all P < 0.05). The higher tertile of pGFAP was associated with greater change in MMSE score and poor cognitive outcome during follow-up both in FTD (1.40 points annually, hazard ratio [HR] 3.82, P < 0.005) and in AD (1.20 points annually, HR 2.26, P < 0.005).ConclusionspGFAP and pNfL levels differ in FTD and AD, and their combination is useful for distinguishing between the two diseases. pGFAP could also be used to track disease severity and predict greater cognitive decline during follow-up in patients with FTD.

【 授权许可】

CC BY