Evidence map›Paper›PMID 35041990›Full record

ReviewNeurobiology of disease2022

Soluble TREM2: Innocent bystander or active player in neurological diseases?

Fabia Filipello, Claire Goldsbury, Shih Feng You, Alberto Locca, Celeste M Karch, Laura Piccio

Open access · goldAbstract readReview
In one paragraph

Review in Neurobiology of disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
82citing papers in PubMed, 2 pooled it
10.1field-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

82 citing papers in PubMed, 2 syntheses or guidelines pooled it, 125 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Review
  16. Review
  17. Review
  18. Pediatric discovery · 2025
    Article
  19. Article
  20. Review

22 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

6 authors at 3 institutions in 2 countries.

Fabia FilipelloDepartment of Neurology, Washington University School of Medicine, St. Louis, MO, USA; Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
Claire GoldsburyBrain and Mind Centre and Charles Perkins Centre, School of Medical Sciences, University of Sydney, Sydney, NSW 2050, Australia.
Shih Feng YouDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
Alberto LoccaDepartment of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
Celeste M KarchDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA.
Laura PiccioDepartment of Neurology, Washington University School of Medicine, St. Louis, MO, USA; Brain and Mind Centre and Charles Perkins Centre, School of Medical Sciences, University of Sydney, Sydney, NSW 2050, Australia; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: picciol@wustl.edu.
Washington University in St. Louis · USHope Center for Neurological Disorders · USUniversity of Sydney · AU

Funding

GENETIC MODIFIERS OF CEREBROSPINAL FLUID TREM2 IN ALZHEIMER'S DISEASERF1AG058501 · NIA · WASHINGTON UNIVERSITY · PI CRUCHAGA, CARLOS, PICCIO, LAURA · 2018 to 2018
$3.5M
Defining the Mechanisms by Which MS4A Genes Regulate TREM2 in Alzheimer DiseaseR01AG062734 · NIA · WASHINGTON UNIVERSITY · PI KARCH, CELESTE MARIE · 2019 to 2023
$3.0M
Genetic Modifiers of TREM2 in Alzheimer's DiseaseR01AG058501 · NIA · WASHINGTON UNIVERSITY · PI Carlos Cruchaga · 2024 to 2026
$2.2M
NIA NIH HHS R01 AG058501NIA NIH HHS R01 AG062734NIA NIH HHS RF1 AG058501
6 · The paper itself

Abstract

Triggering receptor expressed on myeloid cells 2 (TREM2) is an innate immune receptor expressed by macrophages and microglia in the central nervous system (CNS). TREM2 has attracted a lot of interest in the past decade for its critical role in modulating microglia functions under homeostatic conditions and in neurodegenerative diseases. Genetic variation in TREM2 is sufficient to cause Nasu-Hakola disease, a rare pre-senile dementia with bone cysts, and to increase risk for Alzheimer's disease, frontotemporal dementia, and other neurodegenerative disorders. Beyond the role played by TREM2 genetic variants in these diseases, TREM2 engagement is a key step in microglia activation in response to different types of tissue injury (e.g. β-Amyloid deposition, demyelination, apoptotic cell death) leading to enhanced microglia metabolism, phagocytosis, proliferation and survival. TREM2 also exists as a soluble form (sTREM2), generated from receptor shedding or alternative splicing, which is detectable in plasma and cerebrospinal fluid (CSF). Genetic variation, physiological conditions and disease status impact CSF sTREM2 levels. Clinical and preclinical studies suggest that targeting and/or monitoring sTREM2 could have clinical and therapeutic implications. Despite the critical role of sTREM2 in neurologic disease, its function remains poorly understood. Here, we review the current literature on sTREM2 regarding its origin, genetic variation, and possible functions as a biomarker in neurological disorders and as a potential active player in CNS diseases and target for therapies.

Indexed as

Alzheimer DiseaseFrontotemporal DementiaBiomarkersHumansMembrane GlycoproteinsMicrogliaReceptors, ImmunologicBiomarkersMembrane GlycoproteinsReceptors, ImmunologicTREM2 protein, humanMicrogliaNeurodegenerationNeuroinflammationTREM2

Identifiers

PMID35041990
PMCPMC10108835
OpenAlexW4205439582

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.