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

Abstract:

:Our understanding of Alzheimer'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.

journal_name

Nat Med

journal_title

Nature medicine

authors

Johnson ECB,Dammer EB,Duong DM,Ping L,Zhou M,Yin L,Higginbotham LA,Guajardo A,White B,Troncoso JC,Thambisetty M,Montine TJ,Lee EB,Trojanowski JQ,Beach TG,Reiman EM,Haroutunian V,Wang M,Schadt E,Zhang B,Dickson DW

doi

10.1038/s41591-020-0815-6

subject

Has Abstract

pub_date

2020-05-01 00:00:00

pages

769-780

issue

5

eissn

1078-8956

issn

1546-170X

pii

10.1038/s41591-020-0815-6

journal_volume

26

pub_type

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