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A data-driven disease progression model of fluid biomarkers in genetic frontotemporal dementia
Brain  (IF13.501),  Pub Date : 2021-10-11, DOI: 10.1093/brain/awab382
Emma L van der Ende, Esther E Bron, Jackie M Poos, Lize C Jiskoot, Jessica L Panman, Janne M Papma, Lieke H Meeter, Elise G P Dopper, Carlo Wilke, Matthis Synofzik, Carolin Heller, Imogen J Swift, Aitana Sogorb-Esteve, Arabella Bouzigues, Barbara Borroni, Raquel Sanchez-Valle, Fermin Moreno, Caroline Graff, Robert Laforce, Daniela Galimberti, Mario Masellis, Maria Carmela Tartaglia, Elizabeth Finger, Rik Vandenberghe, James B Rowe, Alexandre de Mendonça, Fabrizio Tagliavini, Isabel Santana, Simon Ducharme, Christopher R Butler, Alexander Gerhard, Johannes Levin, Adrian Danek, Markus Otto, Yolande A L Pijnenburg, Sandro Sorbi, Henrik Zetterberg, Wiro J Niessen, Jonathan D Rohrer, Stefan Klein, John C van Swieten, Vikram Venkatraghavan, Harro Seelaar, the GENFI consortium

Several CSF and blood biomarkers for genetic frontotemporal dementia (FTD) have been proposed, including those reflecting neuroaxonal loss (neurofilament light chain (NfL) and phosphorylated neurofilament heavy chain (pNfH)), synapse dysfunction (neuronal pentraxin 2 (NPTX2)), astrogliosis (glial fibrillary acidic protein (GFAP)), and complement activation (C1q, C3b). Determining the sequence in which biomarkers become abnormal over the course of disease could facilitate disease staging and help identify mutation carriers with prodromal or early-stage FTD, which is especially important as pharmaceutical trials emerge. We aimed to model the sequence of biomarker abnormalities in presymptomatic and symptomatic genetic FTD using cross-sectional data from the Genetic Frontotemporal dementia Initiative (GENFI), a longitudinal cohort study.