Proteomics of brain, CSF, and plasma identifies molecular signatures for distinguishing sporadic and genetic Alzheimer's disease.

Autor: Sung YJ; Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63108, USA.; NeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, MO 63108, USA.; Division of Biostatistics, Washington University School of Medicine, St. Louis, MO 63108, USA., Yang C; Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63108, USA.; NeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, MO 63108, USA., Norton J; Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63108, USA.; NeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, MO 63108, USA., Johnson M; Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63108, USA.; NeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, MO 63108, USA., Fagan A; Charles F. and Joanne Knight Alzheimer Disease Research Center, Washington University School of Medicine, St. Louis, MO 63108, USA.; Department of Neurology, Washington University School of Medicine, St. Louis, MO 63108, USA., Bateman RJ; Charles F. and Joanne Knight Alzheimer Disease Research Center, Washington University School of Medicine, St. Louis, MO 63108, USA.; Department of Neurology, Washington University School of Medicine, St. Louis, MO 63108, USA., Perrin RJ; Charles F. and Joanne Knight Alzheimer Disease Research Center, Washington University School of Medicine, St. Louis, MO 63108, USA.; Department of Neurology, Washington University School of Medicine, St. Louis, MO 63108, USA.; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63108, USA., Morris JC; Charles F. and Joanne Knight Alzheimer Disease Research Center, Washington University School of Medicine, St. Louis, MO 63108, USA.; Department of Neurology, Washington University School of Medicine, St. Louis, MO 63108, USA.; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63108, USA., Farlow MR; Department of Neurology, Indiana University School of Medicine, Indianapolis, IN 46202, USA., Chhatwal JP; Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA., Schofield PR; Neuroscience Research Australia, Randwick, NSW 2031, Australia.; School of Biomedical Sciences, University of New South Wales, Sydney, NSW 2052, Australia., Chui H; Department of Neurology, University of Southern California, Los Angeles, CA 90089, USA., Wang F; Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63108, USA.; NeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, MO 63108, USA., Novotny B; Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63108, USA., Eteleeb A; Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63108, USA., Karch C; Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63108, USA.; NeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, MO 63108, USA., Schindler SE; Charles F. and Joanne Knight Alzheimer Disease Research Center, Washington University School of Medicine, St. Louis, MO 63108, USA.; Department of Neurology, Washington University School of Medicine, St. Louis, MO 63108, USA., Rhinn H; Leal Therapeutics, 17 Briden St., Office 329, Worcester, MA 01605, USA., Johnson ECB; Goizueta Alzheimer's Disease Research Center, Emory University School of Medicine, Atlanta, GA 30329, USA., Oh HS; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94304, USA., Rutledge JE; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94304, USA., Dammer EB; Goizueta Alzheimer's Disease Research Center, Emory University School of Medicine, Atlanta, GA 30329, USA., Seyfried NT; Goizueta Alzheimer's Disease Research Center, Emory University School of Medicine, Atlanta, GA 30329, USA.; Department of Biochemistry, Emory School of Medicine, Atlanta, GA 30329, USA., Wyss-Coray T; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94304, USA., Harari O; Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63108, USA., Cruchaga C; Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63108, USA.; NeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, MO 63108, USA.; Charles F. and Joanne Knight Alzheimer Disease Research Center, Washington University School of Medicine, St. Louis, MO 63108, USA.
Jazyk: angličtina
Zdroj: Science translational medicine [Sci Transl Med] 2023 Jul 05; Vol. 15 (703), pp. eabq5923. Date of Electronic Publication: 2023 Jul 05.
DOI: 10.1126/scitranslmed.abq5923
Abstrakt: Proteomic studies for Alzheimer's disease (AD) are instrumental in identifying AD pathways but often focus on single tissues and sporadic AD cases. Here, we present a proteomic study analyzing 1305 proteins in brain tissue, cerebrospinal fluid (CSF), and plasma from patients with sporadic AD, TREM2 risk variant carriers, patients with autosomal dominant AD (ADAD), and healthy individuals. We identified 8 brain, 40 CSF, and 9 plasma proteins that were altered in individuals with sporadic AD, and we replicated these findings in several external datasets. We identified a proteomic signature that differentiated TREM2 variant carriers from both individuals with sporadic AD and healthy individuals. The proteins associated with sporadic AD were also altered in patients with ADAD, but with a greater effect size. Brain-derived proteins associated with ADAD were also replicated in additional CSF samples. Enrichment analyses highlighted several pathways, including those implicated in AD (calcineurin and Apo E), Parkinson's disease (α-synuclein and LRRK2), and innate immune responses (SHC1, ERK-1, and SPP1). Our findings suggest that combined proteomics across brain tissue, CSF, and plasma can be used to identify markers for sporadic and genetically defined AD.
Databáze: MEDLINE