@article{a720589606c043b2bdf8a722532557cd,
title = "Large-scale proteomic analysis of Alzheimer{\textquoteright}s disease brain and cerebrospinal fluid reveals early changes in energy metabolism associated with microglia and astrocyte activation",
abstract = "Our understanding of Alzheimer{\textquoteright}s disease (AD) pathophysiology remains incomplete. Here we used quantitative mass spectrometry and coexpression network analysis to conduct the largest proteomic study thus far on AD. A protein network module linked to sugar metabolism emerged as one of the modules most significantly associated with AD pathology and cognitive impairment. This module was enriched in AD genetic risk factors and in microglia and astrocyte protein markers associated with an anti-inflammatory state, suggesting that the biological functions it represents serve a protective role in AD. Proteins from this module were elevated in cerebrospinal fluid in early stages of the disease. In this study of >2,000 brains and nearly 400 cerebrospinal fluid samples by quantitative proteomics, we identify proteins and biological processes in AD brains that may serve as therapeutic targets and fluid biomarkers for the disease.",
author = "Johnson, {Erik C.B.} and Dammer, {Eric B.} and Duong, {Duc M.} and Lingyan Ping and Maotian Zhou and Luming Yin and Higginbotham, {Lenora A.} and Andrew Guajardo and Bartholomew White and Troncoso, {Juan C.} and Madhav Thambisetty and Montine, {Thomas J.} and Lee, {Edward B.} and Trojanowski, {John Q.} and Beach, {Thomas G.} and Reiman, {Eric M.} and Vahram Haroutunian and Minghui Wang and Eric Schadt and Bin Zhang and Dickson, {Dennis W.} and Nil{\"u}fer Ertekin-Taner and Golde, {Todd E.} and Petyuk, {Vladislav A.} and {De Jager}, {Philip L.} and Bennett, {David A.} and Wingo, {Thomas S.} and Srikant Rangaraju and Ihab Hajjar and Shulman, {Joshua M.} and Lah, {James J.} and Levey, {Allan I.} and Seyfried, {Nicholas T.}",
note = "Funding Information: We are grateful to those who agreed to donate their brains and CSF for research and who participated in the described observational studies. This study was supported by the following National Institutes of Health funding mechanisms: R01AG053960, R01AG057911, R01AG061800, RF1AG057471, RF1AG057470, R01AG061800, R01AG057911, R01AG057339, U01AG061357, P50AG025688, RF1AG057470, RF1AG051633, P30AG10161, R01AG15819, R01AG17917, U01AG61356, R01AG056533, K08NS099474, U01AG046170, RF1AG054014, RF1AG057440, R01AG057907, U01AG052411, P30AG10124, U01AG046161, R01AG050631, R01AG053960, R01AG057339, U01AG061357, P50AG005146, U24NS072026 and P30AG19610. The study was also supported in part by the intramural program of the National Institute on Aging (NIA). Publisher Copyright: {\textcopyright} 2020, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.",
year = "2020",
month = may,
day = "1",
doi = "10.1038/s41591-020-0815-6",
language = "English",
volume = "26",
pages = "769--780",
journal = "Nature Medicine",
issn = "1078-8956",
publisher = "Nature Publishing Group",
number = "5",
}