Evidence map›Paper›PMID 34767070›Full record

ArticleActa neuropathologica2022

Diverse human astrocyte and microglial transcriptional responses to Alzheimer's pathology.

Amy M Smith, Karen Davey, Stergios Tsartsalis, Combiz Khozoie, Nurun Fancy, See Swee Tang, Eirini Liaptsi, Maria Weinert, Aisling McGarry, Robert C J Muirhead and 3 more

Open access · hybridAbstract read
In one paragraph

Article in Acta neuropathologica, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 132 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
132citing papers in PubMed, 3 pooled it
14.8field-weighted citation impact, top 1% 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

132 citing papers in PubMed, 3 syntheses or guidelines pooled it, 189 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pharmacodynamic effects of semorinemab on plasma and CSF biomarkers of Alzheimer's disease pathophysiology.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024
    Trial
  5. Trial
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Review
  13. Targeting the non-coding RNA-PANoptosis axis: a novel frontier in disease diagnosis and therapy.Apoptosis : an international journal on programmed cell death · 2026
    Review
  14. Article
  15. Review
  16. Review
  17. Article
  18. Article
  19. Article
  20. Article

72 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

13 authors at 2 institutions in 2 countries.

Amy M SmithUK Dementia Research Institute, Imperial College London, London, UK.
Karen DaveyUK Dementia Research Institute, Imperial College London, London, UK.
Stergios TsartsalisE515, Department of Brain Sciences, Imperial College London, Hammersmith Hospital, DuCane Road, London, WC12 0NN, UK.
Combiz KhozoieE515, Department of Brain Sciences, Imperial College London, Hammersmith Hospital, DuCane Road, London, WC12 0NN, UK.
Nurun FancyUK Dementia Research Institute, Imperial College London, London, UK.
See Swee TangE515, Department of Brain Sciences, Imperial College London, Hammersmith Hospital, DuCane Road, London, WC12 0NN, UK.
Eirini LiaptsiE515, Department of Brain Sciences, Imperial College London, Hammersmith Hospital, DuCane Road, London, WC12 0NN, UK.
Maria WeinertE515, Department of Brain Sciences, Imperial College London, Hammersmith Hospital, DuCane Road, London, WC12 0NN, UK.
Aisling McGarryUK Dementia Research Institute, Imperial College London, London, UK.
Robert C J MuirheadUK Dementia Research Institute, Imperial College London, London, UK.
Steve GentlemanE515, Department of Brain Sciences, Imperial College London, Hammersmith Hospital, DuCane Road, London, WC12 0NN, UK.
David R OwenE515, Department of Brain Sciences, Imperial College London, Hammersmith Hospital, DuCane Road, London, WC12 0NN, UK.
Paul M MatthewsUK Dementia Research Institute, Imperial College London, London, UK. p.matthews@imperial.ac.uk.
Imperial College London · GBHammersmith Hospital · GB

Funding

Department of HealthMedical Research Council G0100811Medical Research Council G0300665Medical Research Council G0601966Medical Research Council G0900897Medical Research Council G9409531Medical Research Council G9409634Medical Research Council G9901399Medical Research Council MC_PC_17114Medical Research Council MR/K501013/1Medical Research Council MR/M024903/1Medical Research Council MR/N008219/1Medical Research Council MR/N026934/1Medical Research Council MR/T031891/1
6 · The paper itself

Abstract

To better define roles that astrocytes and microglia play in Alzheimer's disease (AD), we used single-nuclei RNA-sequencing to comprehensively characterise transcriptomes in astrocyte and microglia nuclei selectively enriched during isolation post-mortem from neuropathologically defined AD and control brains with a range of amyloid-beta and phospho-tau (pTau) pathology. Significant differences in glial gene expression (including AD risk genes expressed in both the astrocytes [CLU, MEF2C, IQCK] and microglia [APOE, MS4A6A, PILRA]) were correlated with tissue amyloid or pTau expression. The differentially expressed genes were distinct between with the two cell types and pathologies, although common (but cell-type specific) gene sets were enriched with both pathologies in each cell type. Astrocytes showed enrichment for proteostatic, inflammatory and metal ion homeostasis pathways. Pathways for phagocytosis, inflammation and proteostasis were enriched in microglia and perivascular macrophages with greater tissue amyloid, but IL1-related pathway enrichment was found specifically in association with pTau. We also found distinguishable sub-clusters in the astrocytes and microglia characterised by transcriptional signatures related to either homeostatic functions or disease pathology. Gene co-expression analyses revealed potential functional associations of soluble biomarkers of AD in astrocytes (CLU) and microglia (GPNMB). Our work highlights responses of both astrocytes and microglia for pathological protein clearance and inflammation, as well as glial transcriptional diversity in AD.

Indexed as

AgedAged, 80 and overAlzheimer DiseaseAstrocytesBrainFemaleHumansMaleMicrogliaTranscriptomeAlzheimer’s diseaseAmyloid-betaAstrocytesMicrogliasnRNA sequencingTau

Identifiers

PMID34767070
PMCPMC8732962
OpenAlexW3214651914

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.