Large-scale Proteomic Analysis of Alzheimer's Disease Brain and Cerebrospinal Fluid Reveals Early Changes in Energy Metabolism Associated with Microglia and Astrocyte Activation

Overview

Journal Nat Med

Specialties General Medicine
Molecular Biology

Date 2020 Apr 15

PMID 32284590

Citations 431

Authors

Erik C B Johnson

Eric B Dammer

Duc M Duong

Lingyan Ping

Maotian Zhou

Luming Yin

Lenora A Higginbotham

Andrew Guajardo

Bartholomew White

Juan C Troncoso

Madhav Thambisetty

Thomas J Montine

Edward B Lee

John Q Trojanowski

Thomas G Beach

Eric M Reiman

Vahram Haroutunian

Minghui Wang

Eric Schadt

Bin Zhang

Dennis W Dickson

Nilufer Ertekin-Taner

Todd E Golde

Vladislav A Petyuk

Philip L De Jager

David A Bennett

Thomas S Wingo

Srikant Rangaraju

Ihab Hajjar

Joshua M Shulman

James J Lah

Allan I Levey

Nicholas T Seyfried

Affiliations

Soon will be listed here.

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.

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