Evidence map›Paper›PMID 29954413›Full record

ArticleMolecular neurodegeneration2018

Quantitative proteomics of acutely-isolated mouse microglia identifies novel immune Alzheimer's disease-related proteins.

Srikant Rangaraju, Eric B Dammer, Syed Ali Raza, Tianwen Gao, Hailian Xiao, Ranjita Betarbet, Duc M Duong, James A Webster, Chadwick M Hales, James J Lah and 2 more

Open access · goldAbstract read
In one paragraph

Article in Molecular neurodegeneration, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
80citing papers in PubMed, 1 pooled it
5.8field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

80 citing papers in PubMed, 1 synthesis or guideline pooled it, 159 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. APOE4 disrupts the central dogma by arresting neuronal proteome dynamics.bioRxiv : the preprint server for biology · 2026
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20 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 1 institution in 1 country.

Srikant RangarajuDepartment of Neurology, Emory University, Atlanta, GA, 30322, USA. Srikant.rangaraju@emory.edu.ORCID 0000-0003-2765-1500
Eric B DammerDepartment of Biochemistry, Emory University, Atlanta, GA, 30322, USA.
Syed Ali RazaDepartment of Neurology, Emory University, Atlanta, GA, 30322, USA.
Tianwen GaoDepartment of Neurology, Emory University, Atlanta, GA, 30322, USA.
Hailian XiaoDepartment of Neurology, Emory University, Atlanta, GA, 30322, USA.
Ranjita BetarbetDepartment of Neurology, Emory University, Atlanta, GA, 30322, USA.
Duc M DuongDepartment of Biochemistry, Emory University, Atlanta, GA, 30322, USA.
James A WebsterDepartment of Neurology, Emory University, Atlanta, GA, 30322, USA.
Chadwick M HalesDepartment of Neurology, Emory University, Atlanta, GA, 30322, USA.
James J LahDepartment of Neurology, Emory University, Atlanta, GA, 30322, USA.
Allan I LeveyDepartment of Neurology, Emory University, Atlanta, GA, 30322, USA.
Nicholas T SeyfriedDepartment of Neurology, Emory University, Atlanta, GA, 30322, USA. ntseyfri@emory.edu.
Emory University · US

Funding

The Emory Alzheimer's Disease CenterP50AG025688 · NIA · EMORY UNIVERSITY · PI LEVEY, ALLAN I · 2005 to 2019
$25.7M
Discovery of Novel Proteomic Targets in Alzheimer's DiseaseU01AG046161 · NIA · EMORY UNIVERSITY · PI BENNETT, DAVID ALAN, GESCHWIND, DANIEL H · 2014 to 2018
$8.4M
ENNCF - Viral Vector CoreP30NS055077 · NINDS · EMORY UNIVERSITY · PI RESSLER, KERRY J. · 2008 to 2018
$6.8M
A systems biology approach in Drosophila to identify novel factors that influence AD pathogenicityRF1AG057330 · NIA · UNIVERSITY OF WASHINGTON · PI PROMISLOW, DANIEL EDWARD · 2017 to 2017
$3.4M
Tau-Spliceosome Interactions in Alzheimer's DiseaseR01AG053960 · NIA · BAYLOR COLLEGE OF MEDICINE · PI SEYFRIED, NICHOLAS THOMAS, SHULMAN, JOSHUA M · 2016 to 2020
$3.2M
Brain - Plasma Proteomics Biomarker Discovery and Validation in the US and UKRF1AG057471 · NIA · EMORY UNIVERSITY · PI BENNETT, DAVID ALAN, LEVEY, ALLAN I · 2017 to 2017
$3.2M
Building a high-resolution multi-omic AD interactome with the AMP-AD and M2OVE-AD ProjectsRF1AG057470 · NIA · EMORY UNIVERSITY · PI HAJJAR, IHAB M, SEYFRIED, NICHOLAS THOMAS · 2017 to 2017
$3.1M
Microglial and macrophage potassium channels as regulators of neuroinflammation in Alzheimer's DiseaseK08NS099474 · NINDS · EMORY UNIVERSITY · PI RANGARAJU, SRIKANT · 2016 to 2020
$943k
Investigating RNA splicing factor aggregations in Alzheimer's disease and CTEK08NS087121 · NINDS · EMORY UNIVERSITY · PI HALES, CHADWICK M · 2014 to 2018
$858k
Alzheimer's Association 37102American Brain Foundation #28301NIA NIH HHS P50 AG025688NIA NIH HHS R01 AG053960NIA NIH HHS RF1 AG057330NIA NIH HHS RF1 AG057470NIA NIH HHS RF1 AG057471NIA NIH HHS U01 AG046161NIH HHS R01AG057330NIH HHS RF1AG057470NIH HHS RF1AG057471NIH HHS U01AG046161NINDS NIH HHS K08 NS087121NINDS NIH HHS K08-NS087121NINDS NIH HHS K08 NS099474NINDS NIH HHS K08-NS099474-1NINDS NIH HHS P30 NS055077
6 · The paper itself

Abstract

backgroundMicroglia are innate immune cells of the brain that perform phagocytic and inflammatory functions in disease conditions. Transcriptomic studies of acutely-isolated microglia have provided novel insights into their molecular and functional diversity in homeostatic and neurodegenerative disease states. State-of-the-art mass spectrometry methods can comprehensively characterize proteomic alterations in microglia in neurodegenerative disorders, potentially providing novel functionally relevant molecular insights that are not provided by transcriptomics. However, comprehensive proteomic profiling of adult primary microglia in neurodegenerative disease conditions has not been performed.

methodsWe performed quantitative mass spectrometry based proteomic analyses of purified CD11b

resultsOf 4133 proteins identified, 187 microglial proteins were differentially expressed in the 5xFAD mouse model of AD pathology, including proteins with previously known (Apoe, Clu and Htra1) as well as previously unreported relevance to AD biology (Cotl1 and Hexb). Proteins upregulated in 5xFAD microglia shared significant overlap with pro-inflammatory changes observed in LPS-treated mice. Several proteins increased in human AD brain were also upregulated by 5xFAD microglia (Aβ peptide, Apoe, Htra1, Cotl1 and Clu). Cotl1 was identified as a novel microglia-specific marker with increased expression and strong association with AD neuropathology. Apoe protein was also detected within plaque-associated microglia in which Apoe and Aβ were highly co-localized, suggesting a role for Apoe in phagocytic clearance of Aβ.

conclusionsWe report a comprehensive proteomic study of adult mouse microglia derived from acute neuroinflammation and AD models, representing a valuable resource to the neuroscience research community. We highlight shared and unique microglial proteomic changes in acute neuroinflammation aging and AD mouse models and identify novel roles for microglial proteins in human neurodegeneration.

Indexed as

Alzheimer DiseaseAnimalsFemaleMiceMice, Inbred C57BLMicrogliaProteomicsAlzheimer’s diseaseImmunologyMass spectrometryMicrogliaNeurodegenerationNeuroinflammationProteomics

Identifiers

PMID29954413
PMCPMC6025801
OpenAlexW2811319287

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.