Large-scale proteomic analysis of Alzheimer’s disease brain and cerebrospinal fluid reveals early changes in energy metabolism associated with microglia and astrocyte activation

Johnson, Erik B.; Dammer, Eric B.; Duong, Duc M.; Ping, Lingyan; Zhou, Maotian; Yin, Luming; Higginbotham, Lenora A.; Guajardo, Andrew; White, Bartholomew; Troncoso, Juan C.; Thambisetty, Madhav; Montine, Thomas J.; Lee, Edward B.; Trojanowski, John Q.; Beach, Thomas G.; Reiman, Eric M.; Haroutunian, Vahram; Wang, Minghui; Schadt, Eric; Zhang, Bin; Dickson, Dennis W.; Ertekin-Taner, Nilüfer; Golde, Todd E.; Petyuk, Vladislav A.; De Jager, Philip L.; Bennett, David A.; Wingo, Thomas S.; Rangaraju, Srikant; Hajjar, Ihab; Shulman, Joshua M.; Lah, James J.; Levey, Allan I.; Seyfried, Nicholas T.

doi:10.1038/s41591-020-0815-6

Large-scale proteomic analysis of Alzheimer’s disease brain and cerebrospinal fluid reveals early changes in energy metabolism associated with microglia and astrocyte activation

Journal Article · Mon Apr 13 00:00:00 EDT 2020 · Nature Medicine

DOI:https://doi.org/10.1038/s41591-020-0815-6· OSTI ID:1995091

^[1]; ^[1]; Duong, Duc M. ^[1]; Ping, Lingyan ^[1]; Zhou, Maotian ^[1]; Yin, Luming ^[1]; Higginbotham, Lenora A. ^[1]; Guajardo, Andrew ^[2]; White, Bartholomew ^[2]; Troncoso, Juan C. ^[2]; Thambisetty, Madhav ^[3]; Montine, Thomas J. ^[4]; ^[5]; ^[5]; Beach, Thomas G. ^[6]; ^[7]; ^[8]; Wang, Minghui ^[9]; ^[9]; Zhang, Bin ^[9] more »

Emory Univ. School of Medicine, Atlanta, GA (United States)
Johns Hopkins School of Medicine, Baltimore, MD (United States)
National Institutes of Health (NIH), Bethesda, MD (United States)
Stanford Univ., CA (United States)
Univ. of Pennsylvania, Philadelphia, PA (United States). Perelman School of Medicine
Banner Sun Health Research Institute, Sun City, AZ (United States)
Arizona State Univ., Phoenix, AZ (United States); Univ. of Arizona, Phoenix, AZ (United States)
Icahn School of Medicine at Mount Sinai, New York, NY (United States); JJ Peters VA Medical Center MIRECC, Bronx, NY (United States)
Icahn School of Medicine at Mount Sinai, New York, NY (United States)
Mayo Clinic, Jacksonville, FL (United States)
Univ. of Florida, Gainesville, FL (United States)
Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
Columbia University Irving Medical Center, New York, NY (United States)
Rush University Medical Center, Chicago, IL (United States)
Baylor College of Medicine, Houston, TX (United States); Texas Children’s Hospital, Houston, TX (United States)

Our understanding of Alzheimer’s disease (AD) pathophysiology remains incomplete. Here, for this work, 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.

View Accepted Manuscript (DOE)

Research Organization:: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)

Sponsoring Organization:: National Institutes of Health (NIH); USDOE

Grant/Contract Number:: AC05-76RL01830

OSTI ID:: 1995091

Report Number(s):: PNNL-SA-156646

Journal Information:: Nature Medicine, Journal Name: Nature Medicine Journal Issue: 5 Vol. 26; ISSN 1078-8956

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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proteome informatics
systems analysis

Large-scale proteomic analysis of Alzheimer’s disease brain and cerebrospinal fluid reveals early changes in energy metabolism associated with microglia and astrocyte activation

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