@article{d6d556392f514249a6aa0ab52d71cf1a,
title = "Higher CSF sTNFR1-related proteins associate with better prognosis in very early Alzheimer{\textquoteright}s disease",
abstract = "Neuroinflammation is associated with Alzheimer{\textquoteright}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{\textquoteright}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{\textquoteright}s disease, while higher soluble TREM2 levels associated with slower decline in the dementia stage of Alzheimer{\textquoteright}s disease. These inflammatory proteins thus provide prognostic information independent of established Alzheimer{\textquoteright}s markers.",
keywords = "Aged, Alzheimer Disease/cerebrospinal fluid, Amyloid beta-Peptides/cerebrospinal fluid, Biomarkers/cerebrospinal fluid, Cerebrospinal Fluid Proteins/analysis, Cognitive Dysfunction/pathology, Female, Humans, Male, Membrane Glycoproteins/cerebrospinal fluid, Peptide Fragments/cerebrospinal fluid, Prognosis, Receptors, Immunologic, Receptors, Tumor Necrosis Factor, Type I/cerebrospinal fluid, tau Proteins/cerebrospinal fluid",
author = "{Alzheimer's Disease Neuroimaging Initiative} and Hu, {William T.} and Tugba Ozturk and Alexander Kollhoff and Whitney Wharton and {Christina Howell}, J. and Michael Weiner and Paul Aisen and Ronald Petersen and Jack, {Clifford R.} and William Jagust and Trojanowki, {John Q.} and Toga, {Arthur W.} and Laurel Beckett and Green, {Robert C.} and Saykin, {Andrew J.} and John Morris and Perrin, {Richard J.} and Shaw, {Leslie M.} and Zaven Kachaturian and Maria Carrillo and William Potter and Lisa Barnes and Marie Bernard and Hector Gonz{\'a}lez and Carole Ho and Hsiao, {John K.} and Eliezer Masliah and Donna Masterman and Ozioma Okonkwo and Laurie Ryan and Nina Silverberg and Adam Fleisher and Tom Montine and Kaye, {Jeffrey A.} and Silbert, {Lisa C.} and Schneider, {Lon S.} and Sonia Pawluczyk and Mauricio Becerra and James Brewer and Heidebrink, {Judith L.} and David Knopman and Javier Villanueva-Meyer and Doody, {Rachelle S.} and Kass, {Joseph S.} and Yaakov Stern and Honig, {Lawrence S.} and Akiva Mintz and Beau Ances and Spann, {Bryan M.} and Joseph Masdeu",
note = "Funding Information: Funding: 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. 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{\textquoteright}s Association; Alzheimer{\textquoteright}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). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer{\textquoteright}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. Publisher Copyright: {\textcopyright} 2021, The Author(s).",
year = "2021",
month = jun,
day = "28",
doi = "10.1038/s41467-021-24220-7",
language = "English (US)",
volume = "12",
pages = "4001",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}