Evidence map›Paper›PMID 35895133›Full record

ArticleCellular and molecular life sciences : CMLS2022

Heterozygous expression of the Alzheimer's disease-protective PLCγ2 P522R variant enhances Aβ clearance while preserving synapses.

Shiden Solomon, Nirmal Kumar Sampathkumar, Ivo Carre, Mrityunjoy Mondal, George Chennell, Anthony C Vernon, Marc-David Ruepp, Jacqueline C Mitchell

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

Article in Cellular and molecular life sciences : CMLS, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.9field-weighted citation impact, top 13% 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

13 citing papers in PubMed, 26 citations in OpenAlex.

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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

8 authors at 1 institution in 1 country.

Shiden SolomonDepartment of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. shiden.solomon@kcl.ac.uk.
Nirmal Kumar SampathkumarDepartment of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Ivo CarreDepartment of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Mrityunjoy MondalDepartment of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
George ChennellWohl Cellular Imaging Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Anthony C VernonDepartment of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Marc-David RueppDepartment of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Jacqueline C MitchellDepartment of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. jacqueline.mitchell@kcl.ac.uk.ORCID http://orcid.org/0000-0002-2677-398X
King's College London · GB

Funding

Medical Research Council MR/W006251/1National Centre for the Replacement, Refinement and Reduction of Animals in Research NC/S001506/1
6 · The paper itself

Abstract

backgroundA rare coding variant, P522R, in the phospholipase C gamma 2 (PLCG2) gene has been identified as protective against late-onset Alzheimer's disease (AD), but the mechanism is unknown. PLCG2 is exclusively expressed in microglia within the central nervous system, and altered microglial function has been implicated in the progression of AD.

methodsHealthy control hiPSCs were CRISPR edited to generate cells heterozygous and homozygous for the PLCG2

resultsHeterozygous expression of the P522R variant resulted in increased microglial clearance of Aβ, while preserving synapses. This was associated with the upregulation of a number of genes, including the anti-inflammatory cytokine Il-10, and the synapse-linked CX3CR1, as well as alterations in mitochondrial function, and increased cellular motility. The protective capacity of PLCγ2

conclusionThese findings suggest that PLCγ2

Indexed as

Alzheimer DiseasePhospholipase C gammaAmyloid beta-PeptidesHumansMicrogliaSynapsesAmyloid beta-PeptidesPhospholipase C gammaPLCG2 protein, humanAlzheimer’s diseaseiPSCMicrogliaPLCG2

Identifiers

PMID35895133
PMCPMC9329165
OpenAlexW4288176989

What OpenQuestion holds

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LicenceCC BY
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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.