CSF proteomics identifies early changes in autosomal dominant Alzheimer's disease
Shen, Yuanyan (NeuroGenomics and Informatics. Washington University)
Timsina, Jigyasha (NeuroGenomics and Informatics. Washington University)
Heo, Gyujin (NeuroGenomics and Informatics. Washington University)
Beric, Aleksandra (NeuroGenomics and Informatics. Washington University)
Ali, Muhammad (Washington University School of Medicine)
Wang, Ciyang (NeuroGenomics and Informatics. Washington University)
Yang, Chengran (NeuroGenomics and Informatics. Washington University)
Wang, Yueyao (NeuroGenomics and Informatics. Washington University)
Western, Danie (NeuroGenomics and Informatics. Washington University)
Liu, Menghan (NeuroGenomics and Informatics. Washington University)
Gorijala, Priyanka (NeuroGenomics and Informatics. Washington University)
Budde, John (NeuroGenomics and Informatics. Washington University)
Do, Anh (NeuroGenomics and Informatics. Washington University)
Liu, Haiyan (Department of Neurology. Washington University School of Medicine)
Gordon, Brian (Department of Neurology. Washington University School of Medicine)
Llibre-Guerra, Jorge J. (Department of Neurology. Washington University School of Medicine)
Joseph-Mathurin, Nelly (Mallinckrodt Institute of Radiology. Washington University)
Perrin, Richard J. (Washington University St. Louis)
Maschi, Dario (Department of Cell Biology and Physiology. Washington University St. Louis)
Wyss-Coray, Tony (Department of Neurology & Neurological Sciences. Stanford University)
Pastor, Pau (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Renton, Alan E. (Icahn School of Medicine at Mount Sinai (Nova York, Estats Units d'Amèrica))
Surace, Ezequiel I. (Institute of Neurosciences (INEU-Fleni-CONICET), Buenos Aires)
Johnson, Erik C.B. (Emory University School of Medicine, Atlanta)
Levey, Allan I. (Emory University School of Medicine, Atlanta)
Alvarez, Ignacio (Hospital Universitari MútuaTerrassa (Terrassa, Catalunya))
Levin, Johannes (LMU University Hospital)
Ringman, John M. (Keck School of Medicine at USC, Los Angeles)
Allegri, Ricardo Francisco (Department of Cognitive Neurology, Neuropsychology and Neuropsychiatry, FLENI, Buenos Aires)
Seyfried, Nicholas (Emory University School of Medicine, Atlanta)
Day, Gregg S. (Mayo Clinic in Florida, Jacksonville)
Wu, Qisi (Department of Neurology. The First Affiliated Hospital of Chongqing Medical University)
Fernández, M.Victoria (Fundacio ACE Institut de Neurosciencies Aplicades)
Tarawneh, RRawan (The University of New Mexico)
McDade, Eric (Washington University School of Medicine)
Morris, John C. (Washington University School of Medicine)
Bateman, Randall J. (Washington University School of Medicine)
Goate, Alison (Icahn School of Medicine at Mount Sinai (Nova York, Estats Units d'Amèrica))
Ibanez, Laura (Washington University School of Medicine)
Sung, Yun Ju (Washington University School of Medicine)
Dominantly Inherited Alzheimer Network

Data:	2024
Resum:	In this high-throughput proteomic study of autosomal dominant Alzheimer's disease (ADAD), we sought to identify early biomarkers in cerebrospinal fluid (CSF) for disease monitoring and treatment strategies. We examined CSF proteins in 286 mutation carriers (MCs) and 177 non-carriers (NCs). The developed multi-layer regression model distinguished proteins with different pseudo-trajectories between these groups. We validated our findings with independent ADAD as well as sporadic AD datasets and employed machine learning to develop and validate predictive models. Our study identified 137 proteins with distinct trajectories between MCs and NCs, including eight that changed before traditional AD biomarkers. These proteins are grouped into three stages: early stage (stress response, glutamate metabolism, neuron mitochondrial damage), middle stage (neuronal death, apoptosis), and late presymptomatic stage (microglial changes, cell communication). The predictive model revealed a six-protein subset that more effectively differentiated MCs from NCs, compared with conventional biomarkers.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	Cell, Vol. 187 Núm. 22 (Oct. 2024) , p. 6309-6326, ISSN 1097-4172

DOI: 10.1016/j.cell.2024.08.049
PMID: 39332414

34 p, 10.8 MB

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Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
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