Evidence map›Paper›PMID 37591465›Full record

ArticleNeurobiology of disease2023

Alzheimer risk-increasing TREM2 variant causes aberrant cortical synapse density and promotes network hyperexcitability in mouse models.

Melanie Das, Wenjie Mao, Yuliya Voskobiynyk, Deanna Necula, Irene Lew, Cathrine Petersen, Allie Zahn, Gui-Qiu Yu, Xinxing Yu, Nicholas Smith and 4 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurobiology of disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
3.8field-weighted citation impact, top 6% 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

19 citing papers in PubMed, 31 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Roles of TREM2 in Alzheimer's disease.Translational neurodegeneration · 2025
    Review
  5. Article
  6. Review
  7. Review
  8. Article
  9. Neuroinflammation in Alzheimer disease.Nature reviews. Immunology · 2025
    Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. Review
  15. Review
  16. Review
  17. Review
  18. Review
  19. 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

14 authors at 3 institutions in 1 country.

Melanie DasGladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA 94158, USA.
Wenjie MaoGladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA 94158, USA.
Yuliya VoskobiynykGladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA 94158, USA.
Deanna NeculaGladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA 94158, USA; Neuroscience Graduate Program, University of California, San Francisco, CA 94158, USA.
Irene LewGladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA 94158, USA.
Cathrine PetersenGladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA 94158, USA; Neuroscience Graduate Program, University of California, San Francisco, CA 94158, USA.
Allie ZahnGladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA 94158, USA.
Gui-Qiu YuGladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA 94158, USA.
Xinxing YuGladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA 94158, USA.
Nicholas SmithGladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA 94158, USA.
Faten A SayedGladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA 94158, USA.
Li GanHelen and Robert Appel Alzheimer's Disease Research Institute, Weill Cornell Medicine, New York City, NY 10065, USA.
Jeanne T PazGladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA 94158, USA; Neuroscience Graduate Program, University of California, San Francisco, CA 94158, USA; Department of Neurology and Weill Institute for Neurosciences, University of California, San Francisco, CA 94158, USA.
Lennart MuckeGladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA 94158, USA; Neuroscience Graduate Program, University of California, San Francisco, CA 94158, USA; Department of Neurology and Weill Institute for Neurosciences, University of California, San Francisco, CA 94158, USA. Electronic address: lennart.mucke@gladstone.ucsf.edu.
Gladstone Institutes · USUniversity of California, San Francisco · USWeill Cornell Medicine · US

Funding

Neural network and immune cell dysfunctions in Alzheimer's disease pathogenesisRF1AG063519 · NIA · J. DAVID GLADSTONE INSTITUTES · PI MUCKE, LENNART · 2019 to 2020
$5.0M
Deconstructing epileptic circuits in a mouse model of SLC6A1 syndromeF32NS127998 · NINDS · J. DAVID GLADSTONE INSTITUTES · PI VOSKOBIYNYK, YULIYA · 2022 to 2024
$104k
NIA NIH HHS RF1 AG063519NINDS NIH HHS F32 NS127998
6 · The paper itself

Abstract

The R47H variant of triggering receptor expressed on myeloid cells 2 (TREM2) increases the risk of Alzheimer's disease (AD). To investigate potential mechanisms, we analyzed knockin mice expressing human TREM2-R47H from one mutant mouse Trem2 allele. TREM2-R47H mice showed increased seizure activity in response to an acute excitotoxin challenge, compared to wildtype controls or knockin mice expressing the common variant of human TREM2. TREM2-R47H also increased spontaneous thalamocortical epileptiform activity in App knockin mice expressing amyloid precursor proteins bearing autosomal dominant AD mutations and a humanized amyloid-β sequence. In mice with or without such App modifications, TREM2-R47H increased the density of putative synapses in cortical regions without amyloid plaques. TREM2-R47H did not affect synaptic density in hippocampal regions with or without plaques. We conclude that TREM2-R47H increases AD-related network hyperexcitability and that it may do so, at least in part, by causing an imbalance in synaptic densities across brain regions.

Indexed as

Alzheimer DiseaseAllelesAmyloid beta-PeptidesAnimalsDisease Models, AnimalHumansMembrane GlycoproteinsMicePlaque, AmyloidReceptors, ImmunologicSeizuresSynapsesAmyloid beta-PeptidesMembrane GlycoproteinsReceptors, ImmunologicTREM2 protein, humanTrem2 protein, mouseAlzheimer's diseaseAmyloid precursor proteinEEGEpilepsyGliaHyperexcitabilityMicrogliaNetwork dysfunctionSynapsesTREM2

Identifiers

PMID37591465
PMCPMC10681293
OpenAlexW4385830484

What OpenQuestion holds

Textmetadata
LicenceTDM
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.