Integrative proteomics identifies a conserved Aβ amyloid responsome, novel plaque proteins, and pathology modifiers in Alzheimer's disease.

Autor:	Levites Y; Department of Pharmacology and Chemical Biology, School of Medicine, Emory University, Atlanta, GA, USA; Goizueta Brain Health Institute and Alzheimer's Disease Research Center, Emory University School of Medicine, Atlanta, GA, USA; Center for Neurodegenerative Disease Center, Emory University School of Medicine, Atlanta, GA, USA., Dammer EB; Department of Biochemistry, School of Medicine, Emory University, Atlanta, GA, USA; Goizueta Brain Health Institute and Alzheimer's Disease Research Center, Emory University School of Medicine, Atlanta, GA, USA; Center for Neurodegenerative Disease Center, Emory University School of Medicine, Atlanta, GA, USA., Ran Y; Department of Pharmacology and Chemical Biology, School of Medicine, Emory University, Atlanta, GA, USA; Goizueta Brain Health Institute and Alzheimer's Disease Research Center, Emory University School of Medicine, Atlanta, GA, USA; Center for Neurodegenerative Disease Center, Emory University School of Medicine, Atlanta, GA, USA., Tsering W; Department of Pathology, College of Medicine, University of Florida, Gainesville, FL, USA; Evelyn F. and William L. McKnight Brain Institute, University of Florida, Gainesville, FL, USA; Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL, USA., Duong D; Department of Biochemistry, School of Medicine, Emory University, Atlanta, GA, USA; Goizueta Brain Health Institute and Alzheimer's Disease Research Center, Emory University School of Medicine, Atlanta, GA, USA; Center for Neurodegenerative Disease Center, Emory University School of Medicine, Atlanta, GA, USA., Abreha M; Department of Biochemistry, School of Medicine, Emory University, Atlanta, GA, USA; Goizueta Brain Health Institute and Alzheimer's Disease Research Center, Emory University School of Medicine, Atlanta, GA, USA; Center for Neurodegenerative Disease Center, Emory University School of Medicine, Atlanta, GA, USA., Gadhavi J; Department of Biochemistry, School of Medicine, Emory University, Atlanta, GA, USA; Goizueta Brain Health Institute and Alzheimer's Disease Research Center, Emory University School of Medicine, Atlanta, GA, USA; Center for Neurodegenerative Disease Center, Emory University School of Medicine, Atlanta, GA, USA., Lolo K; Department of Pathology, College of Medicine, University of Florida, Gainesville, FL, USA; Evelyn F. and William L. McKnight Brain Institute, University of Florida, Gainesville, FL, USA; Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL, USA., Trejo-Lopez J; Department of Pathology, College of Medicine, University of Florida, Gainesville, FL, USA; Evelyn F. and William L. McKnight Brain Institute, University of Florida, Gainesville, FL, USA; Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL, USA., Phillips J; Department of Pathology, College of Medicine, University of Florida, Gainesville, FL, USA; Evelyn F. and William L. McKnight Brain Institute, University of Florida, Gainesville, FL, USA; Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL, USA., Iturbe A; Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL, USA; Department of Neuroscience, College of Medicine, University of Florida, Gainesville, FL, USA., Erquizi A; Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL, USA; Department of Neuroscience, College of Medicine, University of Florida, Gainesville, FL, USA., Moore BD; Department of Pharmacology and Chemical Biology, School of Medicine, Emory University, Atlanta, GA, USA; Goizueta Brain Health Institute and Alzheimer's Disease Research Center, Emory University School of Medicine, Atlanta, GA, USA; Center for Neurodegenerative Disease Center, Emory University School of Medicine, Atlanta, GA, USA., Ryu D; Department of Pharmacology and Chemical Biology, School of Medicine, Emory University, Atlanta, GA, USA; Goizueta Brain Health Institute and Alzheimer's Disease Research Center, Emory University School of Medicine, Atlanta, GA, USA; Center for Neurodegenerative Disease Center, Emory University School of Medicine, Atlanta, GA, USA., Natu A; Department of Biochemistry, School of Medicine, Emory University, Atlanta, GA, USA; Goizueta Brain Health Institute and Alzheimer's Disease Research Center, Emory University School of Medicine, Atlanta, GA, USA; Center for Neurodegenerative Disease Center, Emory University School of Medicine, Atlanta, GA, USA., Dillon K; Evelyn F. and William L. McKnight Brain Institute, University of Florida, Gainesville, FL, USA; Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL, USA; Department of Neuroscience, College of Medicine, University of Florida, Gainesville, FL, USA., Torrellas J; Evelyn F. and William L. McKnight Brain Institute, University of Florida, Gainesville, FL, USA; Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL, USA; Department of Neuroscience, College of Medicine, University of Florida, Gainesville, FL, USA., Moran C; Evelyn F. and William L. McKnight Brain Institute, University of Florida, Gainesville, FL, USA; Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL, USA; Department of Neuroscience, College of Medicine, University of Florida, Gainesville, FL, USA., Ladd T; Evelyn F. and William L. McKnight Brain Institute, University of Florida, Gainesville, FL, USA; Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL, USA., Afroz F; Department of Pharmacology and Chemical Biology, School of Medicine, Emory University, Atlanta, GA, USA; Goizueta Brain Health Institute and Alzheimer's Disease Research Center, Emory University School of Medicine, Atlanta, GA, USA; Center for Neurodegenerative Disease Center, Emory University School of Medicine, Atlanta, GA, USA., Islam T; Department of Pharmacology and Chemical Biology, School of Medicine, Emory University, Atlanta, GA, USA; Goizueta Brain Health Institute and Alzheimer's Disease Research Center, Emory University School of Medicine, Atlanta, GA, USA; Center for Neurodegenerative Disease Center, Emory University School of Medicine, Atlanta, GA, USA., Jagirdar J; Department of Pathology and Laboratory Medicine, Emory University Hospital, Atlanta, GA, USA., Funk CC; Institute for Systems Biology, Seattle, WA, USA., Robinson M; Institute for Systems Biology, Seattle, WA, USA., Rangaraju S; Department of Neurology, Yale University, New Haven, CT, USA., Borchelt DR; Evelyn F. and William L. McKnight Brain Institute, University of Florida, Gainesville, FL, USA; Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL, USA; Department of Neuroscience, College of Medicine, University of Florida, Gainesville, FL, USA., Ertekin-Taner N; Mayo Clinic, Department of Neuroscience, Jacksonville, FL, USA; Mayo Clinic, Department of Neurology, Jacksonville, FL, USA., Kelly JW; Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA, USA., Heppner FL; Department of Neuropathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 110117 Berlin, Germany; German Center for Neurodegenerative Diseases (DZNE) Berlin, 110117 Berlin, Germany; Cluster of Excellence, NeuroCure, Charitéplatz, 110117 Berlin, Germany., Johnson ECB; Department of Neurology, School of Medicine, Emory University, Atlanta, GA, USA; Goizueta Brain Health Institute and Alzheimer's Disease Research Center, Emory University School of Medicine, Atlanta, GA, USA; Center for Neurodegenerative Disease Center, Emory University School of Medicine, Atlanta, GA, USA., McFarland K; Department of Pharmacology and Chemical Biology, School of Medicine, Emory University, Atlanta, GA, USA; Goizueta Brain Health Institute and Alzheimer's Disease Research Center, Emory University School of Medicine, Atlanta, GA, USA; Center for Neurodegenerative Disease Center, Emory University School of Medicine, Atlanta, GA, USA., Levey AI; Department of Neurology, School of Medicine, Emory University, Atlanta, GA, USA; Goizueta Brain Health Institute and Alzheimer's Disease Research Center, Emory University School of Medicine, Atlanta, GA, USA; Center for Neurodegenerative Disease Center, Emory University School of Medicine, Atlanta, GA, USA., Prokop S; Department of Pathology, College of Medicine, University of Florida, Gainesville, FL, USA; Evelyn F. and William L. McKnight Brain Institute, University of Florida, Gainesville, FL, USA; Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL, USA; Department of Neurology, College of Medicine, University of Florida, Gainesville, FL, USA. Electronic address: sprokop@ufl.edu., Seyfried NT; Department of Biochemistry, School of Medicine, Emory University, Atlanta, GA, USA; Goizueta Brain Health Institute and Alzheimer's Disease Research Center, Emory University School of Medicine, Atlanta, GA, USA; Center for Neurodegenerative Disease Center, Emory University School of Medicine, Atlanta, GA, USA. Electronic address: nseyfri@emory.edu., Golde TE; Department of Pharmacology and Chemical Biology, School of Medicine, Emory University, Atlanta, GA, USA; Department of Neurology, School of Medicine, Emory University, Atlanta, GA, USA; Goizueta Brain Health Institute and Alzheimer's Disease Research Center, Emory University School of Medicine, Atlanta, GA, USA; Center for Neurodegenerative Disease Center, Emory University School of Medicine, Atlanta, GA, USA. Electronic address: tgolde@emory.edu.
Jazyk:	angličtina
Zdroj:	Cell reports. Medicine [Cell Rep Med] 2024 Aug 20; Vol. 5 (8), pp. 101669. Date of Electronic Publication: 2024 Aug 09.
DOI:	10.1016/j.xcrm.2024.101669
Abstrakt:	Alzheimer's disease (AD) is a complex neurodegenerative disorder that develops over decades. AD brain proteomics reveals vast alterations in protein levels and numerous altered biologic pathways. Here, we compare AD brain proteome and network changes with the brain proteomes of amyloid β (Aβ)-depositing mice to identify conserved and divergent protein networks with the conserved networks identifying an Aβ amyloid responsome. Proteins in the most conserved network (M42) accumulate in plaques, cerebrovascular amyloid (CAA), and/or dystrophic neuronal processes, and overexpression of two M42 proteins, midkine (Mdk) and pleiotrophin (PTN), increases the accumulation of Aβ in plaques and CAA. M42 proteins bind amyloid fibrils in vitro, and MDK and PTN co-accumulate with cardiac transthyretin amyloid. M42 proteins appear intimately linked to amyloid deposition and can regulate amyloid deposition, suggesting that they are pathology modifiers and thus putative therapeutic targets. We posit that amyloid-scaffolded accumulation of numerous M42+ proteins is a central mechanism mediating downstream pathophysiology in AD. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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