Evidence map›Paper›PMID 34266459›Full record

ArticleMolecular neurodegeneration2021

Knock-in models related to Alzheimer's disease: synaptic transmission, plaques and the role of microglia.

Diana P Benitez, Shenyi Jiang, Jack Wood, Rui Wang, Chloe M Hall, Carlijn Peerboom, Natalie Wong, Katie M Stringer, Karina S Vitanova, Victoria C Smith and 10 more

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

Article in Molecular neurodegeneration, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed, 2 pooled it
6.0field-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

43 citing papers in PubMed, 2 syntheses or guidelines pooled it, 76 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
  4. Article
  5. Article
  6. Decoding the mechanisms of amyloid-β in synaptic toxicity.Journal of Alzheimer's disease : JAD · 2026
    Review
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  8. Article
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  11. Article
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  13. Lifespan of male and female APP/PS1 and APPJournal of Alzheimer's disease : JAD · 2025
    Article
  14. Article
  15. Review
  16. Article
  17. Review
  18. AnCurrent Alzheimer research · 2025
    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

20 authors at 9 institutions in 9 countries.

Diana P BenitezDepartment of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London, WC1E 6BT, UK.
Shenyi JiangDepartment of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London, WC1E 6BT, UK.
Jack WoodDepartment of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London, WC1E 6BT, UK.
Rui WangDepartment of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London, WC1E 6BT, UK.
Chloe M HallDepartment of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London, WC1E 6BT, UK.
Carlijn PeerboomDepartment of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London, WC1E 6BT, UK.
Natalie WongDepartment of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London, WC1E 6BT, UK.
Katie M StringerDepartment of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London, WC1E 6BT, UK.
Karina S VitanovaDepartment of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London, WC1E 6BT, UK.
Victoria C SmithDepartment of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London, WC1E 6BT, UK.
Dhaval JoshiDepartment of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London, WC1E 6BT, UK.
Takashi SaitoLaboratory for Proteolytic Neuroscience, RIKEN Center for Brain Science, 2-1 Wako-shi, Saitama, 351-0198, Japan.
Takaomi C SaidoLaboratory for Proteolytic Neuroscience, RIKEN Center for Brain Science, 2-1 Wako-shi, Saitama, 351-0198, Japan.
John HardyDementia Research Institute, University College London, Gower Street, London, WC1E 6BT, UK.
Jörg HanriederDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Bart De StrooperDementia Research Institute, University College London, Gower Street, London, WC1E 6BT, UK.
Dervis A SalihDepartment of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London, WC1E 6BT, UK.
Takshashila TripathiDepartment of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London, WC1E 6BT, UK.
Frances A EdwardsDepartment of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London, WC1E 6BT, UK. f.a.edwards@ucl.ac.uk.
Damian M CummingsDepartment of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London, WC1E 6BT, UK. d.cummings@ucl.ac.uk.ORCID http://orcid.org/0000-0001-5567-0907
University College London · GBRIKEN Center for Brain Science · JPUK Dementia Research Institute · GBAllen Institute for Brain Science · USNational Hospital for Neurology and Neurosurgery · GBQueen Mary University of London · GBUniversität Hamburg · DEUniversity of Cambridge · GBUtrecht University · NL

Funding

Medical Research Council G0701075Medical Research Council G0901254Medical Research Council G1001253Medical Research Council MR/J004758/1Medical Research Council MR/K01417X/1Medical Research Council MR/L501542/1Medical Research Council MR/N013867/1Parkinson's UK G-0907Parkinson's UK G-1307
6 · The paper itself

Abstract

backgroundMicroglia are active modulators of Alzheimer's disease but their role in relation to amyloid plaques and synaptic changes due to rising amyloid beta is unclear. We add novel findings concerning these relationships and investigate which of our previously reported results from transgenic mice can be validated in knock-in mice, in which overexpression and other artefacts of transgenic technology are avoided.

methodsApp

resultsBoth App knock-in lines showed increased glutamate release probability prior to detection of plaques. Consistent with results in transgenic mice, this persisted throughout life in App

conclusionsIncreased glutamate release probability is similar across knock-in and transgenic mouse models of Alzheimer's disease, likely reflecting acute physiological effects of soluble amyloid beta. Microglia respond later to increased amyloid beta levels by proliferating and upregulating Cd68 and Trem2. Partial depletion of microglia suggests that, in wild type mice, alteration of surviving phagocytic microglia, rather than microglial loss, drives age-dependent effects on glutamate release that become exacerbated in Alzheimer's disease.

Indexed as

Alzheimer DiseaseDisease Models, AnimalAmyloid beta-Protein PrecursorAnimalsGene Knock-In TechniquesHumansMiceMicrogliaPlaque, AmyloidSynaptic TransmissionAmyloid beta-Protein PrecursorAgeingAlzheimer’s diseaseAmyloid betaGene expressionMicrogliaNeurodegenerationPlaquesSynaptic plasticitySynaptic transmissionTREM2

Identifiers

PMID34266459
PMCPMC8281661
OpenAlexW3182436899

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.