Evidence map›Paper›PMID 34464705›Full record

ArticleNeurobiology of disease2021

Amyloid beta acts synergistically as a pro-inflammatory cytokine.

Thomas J LaRocca, Alyssa N Cavalier, Christine M Roberts, Maddie R Lemieux, Pooja Ramesh, Micklaus A Garcia, Christopher D Link

Open access · goldAbstract read
In one paragraph

Article in Neurobiology of disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed, 4 pooled it
5.6field-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

49 citing papers in PubMed, 4 syntheses or guidelines pooled it, 70 citations in OpenAlex.

  1. Pooled it
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  3. Pooled it
  4. Pooled it
  5. Review
  6. Article
  7. Article
  8. TREM2 in neurodegeneration and diseases.Molecular psychiatry · 2026
    Review
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  13. Article
  14. Longitudinal MRI Characterization of TNMR in biomedicine · 2026
    Article
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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

7 authors at 2 institutions in 1 country.

Thomas J LaRoccaDepartment of Integrative Physiology, University of Colorado Boulder, Boulder, CO, United States of America; Department of Health and Exercise Science, Center for Healthy Aging, Colorado State University (Current), Fort Collins, CO, United States of America. Electronic address: tom.larocca@colostate.edu.
Alyssa N CavalierDepartment of Integrative Physiology, University of Colorado Boulder, Boulder, CO, United States of America; Department of Health and Exercise Science, Center for Healthy Aging, Colorado State University (Current), Fort Collins, CO, United States of America.
Christine M RobertsDepartment of Integrative Physiology, University of Colorado Boulder, Boulder, CO, United States of America.
Maddie R LemieuxDepartment of Integrative Physiology, University of Colorado Boulder, Boulder, CO, United States of America.
Pooja RameshDepartment of Integrative Physiology, University of Colorado Boulder, Boulder, CO, United States of America.
Micklaus A GarciaDepartment of Integrative Physiology, University of Colorado Boulder, Boulder, CO, United States of America.
Christopher D LinkDepartment of Integrative Physiology, University of Colorado Boulder, Boulder, CO, United States of America. Electronic address: linkc@colorado.edu.
University of Colorado Boulder · USColorado State University · US

Funding

TDP-43, RNA Metabolism, and ALS/FTD PathologyR01NS063964 · NINDS · UNIVERSITY OF COLORADO · PI LINK, CHRISTOPHER D. · 2009 to 2019
$3.5M
NINDS NIH HHS R01 NS063964
6 · The paper itself

Abstract

The amyloid beta (Aβ) peptide is believed to play a central role in Alzheimer's disease (AD), the most common age-related neurodegenerative disorder. However, the natural, evolutionarily selected functions of Aβ are incompletely understood. Here, we report that nanomolar concentrations of Aβ act synergistically with known cytokines to promote pro-inflammatory activation in primary human astrocytes (a cell type increasingly implicated in brain aging and AD). Using transcriptomics (RNA-seq), we show that Aβ can directly substitute for the complement component C1q in a cytokine cocktail previously shown to induce astrocyte immune activation. Furthermore, we show that astrocytes synergistically activated by Aβ have a transcriptional signature similar to neurotoxic "A1" astrocytes known to accumulate with age and in AD. Interestingly, we find that this biological action of Aβ at low concentrations is distinct from the transcriptome changes induced by the high/supraphysiological doses of Aβ often used in in vitro studies. Collectively, our results suggest an important, cytokine-like function for Aβ and a novel mechanism by which it may directly contribute to the neuroinflammation associated with brain aging and AD.

Indexed as

AgingAlzheimer DiseaseAmyloid beta-PeptidesAstrocytesBrainComplement C1qCytokinesGene Expression ProfilingHumansInterleukin-1alphaNeuroinflammatory DiseasesPeptide FragmentsPrimary Cell CultureRNA-SeqTumor Necrosis Factor-alphaAmyloid beta-Peptidesamyloid beta-protein (1-42)Complement C1qCytokinesInterleukin-1alphaPeptide FragmentsTumor Necrosis Factor-alphaAlzheimer's diseaseAmyloid betaAstrocytesInflammationTranscriptomics

Identifiers

PMID34464705
PMCPMC8502211
OpenAlexW3196916687

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.