Evidence map›Paper›PMID 39300502›Full record

ArticleActa neuropathologica communications2024

Trem2-deficiency aggravates and accelerates age-related myelin degeneration.

Tyler J McCray, Logan M Bedford, Stephanie J Bissel, Bruce T Lamb

Abstract read
In one paragraph

Article in Acta neuropathologica communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
–field-weighted citation impact
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

16 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. iScience · 2026
    Article
  9. Review
  10. Article
  11. Review
  12. Trem2bioRxiv : the preprint server for biology · 2025
    Article
  13. Article
  14. PLCG2 modulates TREM2 expression and signaling in response to Alzheimer's disease pathology.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
  15. Review
  16. Review
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

4 authors.

Tyler J McCrayStark Neurosciences Research Institute, Indiana University, School of Medicine, Indianapolis, IN 46202, USA.
Logan M BedfordStark Neurosciences Research Institute, Indiana University, School of Medicine, Indianapolis, IN 46202, USA.
Stephanie J Bissel *Stark Neurosciences Research Institute, Indiana University, School of Medicine, Indianapolis, IN 46202, USA.
Bruce T Lamb *Stark Neurosciences Research Institute, Indiana University, School of Medicine, Indianapolis, IN 46202, USA. btlamb@iu.edu.ORCID 0000-0002-2070-6540

Funding

The IU/JAX Alzheimer's Disease Precision Models Center: Rat F344U54AG054345 · NIA · INDIANA UNIVERSITY INDIANAPOLIS · PI Gareth R Howell · 2016 to 2026
$95.6M
Central and Peripheral Roles of TREM2 in Alzheimer's DiseaseRF1AG051495 · NIA · INDIANA UNIVERSITY INDIANAPOLIS · PI LAMB, BRUCE T, LANDRETH, GARY E. · 2015 to 2015
$3.6M
Impact of PLCG2 Alzheimer's Disease Risk Variants on Microglia Biology and Disease PathogenesisRF1AG074566 · NIA · INDIANA UNIVERSITY INDIANAPOLIS · PI BISSEL, STEPHANIE J, LAMB, BRUCE T · 2021 to 2021
$2.3M
Modulation of White Matter Damage via TREM2 and Peripheral Immune Cells in Tau PathologiesF31AG074628 · NIA · INDIANA UNIVERSITY INDIANAPOLIS · PI MCCRAY, TYLER · 2022 to 2023
$63k
NIA NIH HHS F31 AG074628NIA NIH HHS RF1 AG051495NIA NIH HHS RF1 AG074566NIA NIH HHS U54 AG054345
6 · The paper itself

Abstract

Aging is the greatest known risk factor for most neurodegenerative diseases. Myelin degeneration is an early pathological indicator of these diseases and a normal part of aging; albeit, to a lesser extent. Despite this, little is known about the contribution of age-related myelin degeneration on neurodegenerative disease. Microglia participate in modulating white matter events from demyelination to remyelination, including regulation of (de)myelination by the microglial innate immune receptor triggering receptor expressed on myeloid cells 2 (TREM2). Here, we demonstrate Trem2-deficiency aggravates and accelerates age-related myelin degeneration in the striatum. We show TREM2 is necessary for remyelination by recruiting reparative glia and mediating signaling that promotes OPC differentiation/maturation. In response to demyelination, TREM2 is required for phagocytosis of large volumes of myelin debris. In addition to lysosomal regulation, we show TREM2 can modify the ER stress response, even prior to overt myelin debris, that prevents lipid accumulation and microglial dysfunction. These data support a role for Trem2-dependent interactions in age-related myelin degeneration and suggest a basis for how early dysfunctional microglia could contribute to disease pathology through insufficent repair, defective phagocytosis, and the ER stress response.

Indexed as

AgingMembrane GlycoproteinsMicrogliaMyelin SheathReceptors, ImmunologicAnimalsDemyelinating DiseasesEndoplasmic Reticulum StressFemaleMaleMiceMice, Inbred C57BLMice, KnockoutPhagocytosisRemyelinationMembrane GlycoproteinsReceptors, ImmunologicTrem2 protein, mouseAgingMicrogliaMyelin degenerationNeurodegenerationTREM2White matter

Identifiers

PMID39300502
PMCPMC11411802

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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.