CSF proteomics identifies early changes in autosomal dominant Alzheimer's disease.

Autor:	Shen Y; Department of Psychiatry, Washington University, St. Louis, MO 63110, USA; NeuroGenomics and Informatics, Washington University, St. Louis, MO 63110, USA., Timsina J; Department of Psychiatry, Washington University, St. Louis, MO 63110, USA; NeuroGenomics and Informatics, Washington University, St. Louis, MO 63110, USA., Heo G; Department of Psychiatry, Washington University, St. Louis, MO 63110, USA; NeuroGenomics and Informatics, Washington University, St. Louis, MO 63110, USA., Beric A; Department of Psychiatry, Washington University, St. Louis, MO 63110, USA; NeuroGenomics and Informatics, Washington University, St. Louis, MO 63110, USA., Ali M; Department of Psychiatry, Washington University, St. Louis, MO 63110, USA; NeuroGenomics and Informatics, Washington University, St. Louis, MO 63110, USA., Wang C; Department of Psychiatry, Washington University, St. Louis, MO 63110, USA; NeuroGenomics and Informatics, Washington University, St. Louis, MO 63110, USA., Yang C; Department of Psychiatry, Washington University, St. Louis, MO 63110, USA; NeuroGenomics and Informatics, Washington University, St. Louis, MO 63110, USA., Wang Y; Department of Psychiatry, Washington University, St. Louis, MO 63110, USA; NeuroGenomics and Informatics, Washington University, St. Louis, MO 63110, USA., Western D; Department of Psychiatry, Washington University, St. Louis, MO 63110, USA; NeuroGenomics and Informatics, Washington University, St. Louis, MO 63110, USA., Liu M; Department of Psychiatry, Washington University, St. Louis, MO 63110, USA; NeuroGenomics and Informatics, Washington University, St. Louis, MO 63110, USA., Gorijala P; Department of Psychiatry, Washington University, St. Louis, MO 63110, USA; NeuroGenomics and Informatics, Washington University, St. Louis, MO 63110, USA., Budde J; Department of Psychiatry, Washington University, St. Louis, MO 63110, USA; NeuroGenomics and Informatics, Washington University, St. Louis, MO 63110, USA., Do A; Department of Psychiatry, Washington University, St. Louis, MO 63110, USA; NeuroGenomics and Informatics, Washington University, St. Louis, MO 63110, USA., Liu H; Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA., Gordon B; Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA., Llibre-Guerra JJ; Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA., Joseph-Mathurin N; Mallinckrodt Institute of Radiology, Washington University St Louis, St Louis, MO 63110, USA., Perrin RJ; Department of Pathology and Immunology, Washington University St. Louis, St. Louis, MO 63110, USA., Maschi D; Department of Cell Biology and Physiology, Washington University St. Louis, St. Louis, MO 63110, USA., Wyss-Coray T; Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA 94305, USA; Department of Neurology & Neurological Sciences, Stanford University, Stanford, CA 94305, USA., Pastor P; Unit of Neurodegenerative Diseases, Department of Neurology, University Hospital Germans Trias i Pujol and The Germans Trias i Pujol Research Institute (IGTP), Badalona, Barcelona 08916, Spain., Renton AE; Ronald M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Surace EI; Laboratory of Neurodegenerative Diseases, Institute of Neurosciences (INEU-Fleni-CONICET), Buenos Aires, Argentina., Johnson ECB; Goizueta Alzheimer's Disease Research Center, Emory University School of Medicine, Atlanta, GA 30307, USA; Department of Neurology, Emory University School of Medicine, Atlanta, GA 30307, USA., Levey AI; Department of Neurology, Emory University School of Medicine, Atlanta, GA 30307, USA., Alvarez I; Department of Neurology, University Hospital Mútua de Terrassa and Fundació Docència i Recerca Mútua de Terrassa, Terrassa 08221, Barcelona, Spain., Levin J; Department of Neurology, LMU University Hospital, LMU Munich, Munich 80336, Germany; German Center for Neurodegenerative Diseases, site Munich, Munich 80336, Germany., Ringman JM; Alzheimer's Disease Research Center, Department of Neurology, Keck School of Medicine at USC, Los Angeles, CA 90033, USA., Allegri RF; Department of Cognitive Neurology, Neuropsychology and Neuropsychiatry, FLENI, Buenos Aires, Argentina., Seyfried N; Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30307, USA., Day GS; Department of Neurology, Mayo Clinic in Florida, Jacksonville, FL 32224, USA., Wu Q; Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China., Fernández MV; Fundacio ACE Institut de Neurosciencies Aplicades, Barcelona 08029, Spain., Tarawneh R; The University of New Mexico, Albuquerque, NM 87131, USA., McDade E; Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA., Morris JC; Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA., Bateman RJ; Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA., Goate A; Ronald M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA., Ibanez L; Department of Psychiatry, Washington University, St. Louis, MO 63110, USA; NeuroGenomics and Informatics, Washington University, St. Louis, MO 63110, USA; Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA., Sung YJ; Department of Psychiatry, Washington University, St. Louis, MO 63110, USA; NeuroGenomics and Informatics, Washington University, St. Louis, MO 63110, USA; Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA., Cruchaga C; Department of Psychiatry, Washington University, St. Louis, MO 63110, USA; NeuroGenomics and Informatics, Washington University, St. Louis, MO 63110, USA; Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: cruchagac@wustl.edu.
Jazyk:	angličtina
Zdroj:	Cell [Cell] 2024 Oct 31; Vol. 187 (22), pp. 6309-6326.e15. Date of Electronic Publication: 2024 Sep 26.
DOI:	10.1016/j.cell.2024.08.049
Abstrakt:	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. Competing Interests: Declaration of interests C.C. has received research support from GSK and EISAI. C.C. is a member of the advisory board of Circular Genomics and owns stocks in these companies. C.C. is on the advisory board of ADmit. J.L. reports speaker fees from Bayer Vital, Biogen, EISAI, TEVA, Zambon, Merck, and Roche; consulting fees from Axon Neuroscience, EISAI, and Biogen; author fees from Thieme medical publishers and W. Kohlhammer GmbH medical publishers; and is inventor in a patent “Oral Phenylbutyrate for Treatment of Human 4-Repeat Tauopathies” (EP 23 156 122.6). He receives compensation for serving as chief medical officer for MODAG GmbH and is a beneficiary of the phantom share program of MODAG GmbH. E.M. reports research support received from NIA (U01AG059798), Anonymous Foundation, GHR, Alzheimer Association, Eli Lilly Eisai, and Hoffmann-La Roche and paid consulting for Eli Lilly, Alector, Alzamend, Sanofi, AstraZeneca, Hoffmann-La Roche, Grifols, and Merck. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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