@article{2008ed5492d34408b46f793c07b81083,
title = "Integrated proteomics reveals brain-based cerebrospinal fluid biomarkers in asymptomatic and symptomatic Alzheimer's disease",
abstract = "Alzheimer's disease (AD) lacks protein biomarkers reflective of its diverse underlying pathophysiology, hindering diagnostic and therapeutic advancements. Here, we used integrative proteomics to identify cerebrospinal fluid (CSF) biomarkers representing a wide spectrum of AD pathophysiology. Multiplex mass spectrometry identified ~3500 and ~12,000 proteins in AD CSF and brain, respectively. Network analysis of the brain proteome resolved 44 biologically diverse modules, 15 of which overlapped with the CSF proteome. CSF AD markers in these overlapping modules were collapsed into five protein panels representing distinct pathophysiological processes. Synaptic and metabolic panels were decreased in AD brain but increased in CSF, while glial-enriched myelination and immunity panels were increased in brain and CSF. The consistency and disease specificity of panel changes were confirmed in >500 additional CSF samples. These panels also identified biological subpopulations within asymptomatic AD. Overall, these results are a promising step toward a network-based biomarker tool for AD clinical applications.",
author = "Lenora Higginbotham and Lingyan Ping and Dammer, {Eric B.} and Duong, {Duc M.} and Maotian Zhou and Marla Gearing and Cheyenne Hurst and Glass, {Jonathan D.} and Factor, {Stewart A.} and Johnson, {Erik C.B.} and Ihab Hajjar and Lah, {James J.} and Levey, {Allan I.} and Seyfried, {Nicholas T.}",
note = "Funding Information: Support for this research was provided by funding from the National Institute on Aging (R01AG053960, R01AG057911, R01AG061800, RF1AG057471, RF1AG057470, R01AG061800, R01AG057911, and R01AG057339), the Accelerating Medicine Partnership for AD (U01AG046161 and U01AG061357), the Emory ADRC (P50AG025688), and the NINDS Emory Neuroscience Core (P30NS055077). Support was also provided by the Foundation for the National Institutes of Health (FNIH). N.T.S. was also supported in part by grants from the Alzheimer's Association (ALZ), Alzheimer's Research UK (ARUK), The Michael J. Fox Foundation for Parkinson's Research (MJFF), and the Weston Brain Institute (11060). Publisher Copyright: Copyright {\textcopyright} 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).",
year = "2020",
month = oct,
day = "21",
doi = "10.1126/sciadv.aaz9360",
language = "English (US)",
volume = "6",
journal = "Science Advances",
issn = "2375-2548",
publisher = "American Association for the Advancement of Science",
number = "43",
}