Higher CSF sTNFR1-related proteins associate with better prognosis in very early Alzheimer's disease

• Type of Material: Article
• Authors: William Hu, Emory University; Tugba Ozturk, Emory University; Alexander Kollhoff, Emory University; Whitney Wharton, Emory University; Christina J Howell, Emory University
• Language: English
• Date: 2021-06-28
• Publisher: NATURE RESEARCH
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2021
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41467-021-24220-7
• Title of Journal or Parent Work: NATURE COMMUNICATIONS
• Volume: 12
• Issue: 1
• Start Page: 4001
• End Page: 4001
• Grant/Funding Information: The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer’s Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California.; ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics.; The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org).; This study is funded by NIH R01 AG 054046, R21 AG 043885, K01AG042498, and Bobbie Bailey Foundation (Atlanta, GA). Data collection and sharing for ADNI is funded by NIH U01 AG024904 and DOD W81XWH-12-2-0012.
• Keywords: NECROSIS-FACTOR-ALPHA; DISINTEGRIN; BIOMARKERS; Multidisciplinary Sciences; BRAIN; SOLUBLE TREM2; EFFLUX; Science & Technology; METALLOPROTEINASE; ECTODOMAIN; COMPOSITE SCORE; Science & Technology - Other Topics; CEREBROSPINAL-FLUID
• Research Categories: Health Sciences, Nursing

Abstract

Neuroinflammation is associated with Alzheimer’s disease, but the application of cerebrospinal fluid measures of inflammatory proteins may be limited by overlapping pathways and relationships between them. In this work, we measure 15 cerebrospinal proteins related to microglial and T-cell functions, and show them to reproducibly form functionally-related groups within and across diagnostic categories in 382 participants from the Alzheimer’s Disease Neuro-imaging Initiative as well participants from two independent cohorts. We further show higher levels of proteins related to soluble tumor necrosis factor receptor 1 are associated with reduced risk of conversion to dementia in the multi-centered (p = 0.027) and independent (p = 0.038) cohorts of people with mild cognitive impairment due to predicted Alzheimer’s disease, while higher soluble TREM2 levels associated with slower decline in the dementia stage of Alzheimer’s disease. These inflammatory proteins thus provide prognostic information independent of established Alzheimer’s markers.