Evidence map›Paper›PMID 32592479›Full record

ArticleHuman molecular genetics2020

PICALM rescues glutamatergic neurotransmission, behavioural function and survival in a Drosophila model of Aβ42 toxicity.

Yifan Yu, Teresa Niccoli, Ziyu Ren, Nathaniel S Woodling, Benjamin Aleyakpo, Gyorgy Szabadkai, Linda Partridge

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

Article in Human molecular genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 1 pooled it
1.3field-weighted citation impact, top 20% 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

9 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Cell type-specific functions of Alzheimer's disease endocytic risk genes.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024
    Review
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  6. Review
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  9. 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

7 authors at 4 institutions in 3 countries.

Yifan YuDepartment of Genetics, Evolution and Environment, Institute of Healthy Ageing, University College London, London WC1E 6BT, UK.
Teresa NiccoliDepartment of Genetics, Evolution and Environment, Institute of Healthy Ageing, University College London, London WC1E 6BT, UK.
Ziyu RenDepartment of Cell and Developmental Biology, Consortium for Mitochondrial Research, University College London, London WC1E 6BT, UK.
Nathaniel S WoodlingDepartment of Genetics, Evolution and Environment, Institute of Healthy Ageing, University College London, London WC1E 6BT, UK.
Benjamin AleyakpoDepartment of Genetics, Evolution and Environment, Institute of Healthy Ageing, University College London, London WC1E 6BT, UK.
Gyorgy SzabadkaiDepartment of Cell and Developmental Biology, Consortium for Mitochondrial Research, University College London, London WC1E 6BT, UK.
Linda PartridgeDepartment of Genetics, Evolution and Environment, Institute of Healthy Ageing, University College London, London WC1E 6BT, UK.
University College London · GBMax Planck Institute for Biology of Ageing · DEUK Dementia Research Institute · GBUniversity of Padua · IT

Funding

Arthritis Research UK ARUK-SRF2018A-003Wellcome TrustWellcome Trust WT098565/Z/12/Z
6 · The paper itself

Abstract

Alzheimer's disease (AD) is the most common form of dementia and the most prevalent neurodegenerative disease. Genome-wide association studies have linked PICALM to AD risk. PICALM has been implicated in Aβ42 production and turnover, but whether it plays a direct role in modulating Aβ42 toxicity remains unclear. We found that increased expression of the Drosophila PICALM orthologue lap could rescue Aβ42 toxicity in an adult-onset model of AD, without affecting Aβ42 level. Imbalances in the glutamatergic system, leading to excessive, toxic stimulation, have been associated with AD. We found that Aβ42 caused the accumulation of presynaptic vesicular glutamate transporter (VGlut) and increased spontaneous glutamate release. Increased lap expression reversed these phenotypes back to control levels, suggesting that lap may modulate glutamatergic transmission. We also found that lap modulated the localization of amphiphysin (Amph), the homologue of another AD risk factor BIN1, and that Amph itself modulated postsynaptic glutamate receptor (GluRII) localization. We propose a model where PICALM modulates glutamatergic transmission, together with BIN1, to ameliorate synaptic dysfunction and disease progression.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesAnimalsBehavior, AnimalCCAAT-Enhancer-Binding Protein-betaDrosophila melanogasterDrosophila ProteinsExcitatory Amino Acid AgentsHumansMonomeric Clathrin Assembly ProteinsNerve Tissue ProteinsPeptide FragmentsReceptors, Ionotropic GlutamateSynaptic TransmissionTranscription FactorsVesicular Glutamate Transport ProteinsamphiphysinAmyloid beta-Peptidesamyloid beta-protein (1-42)bicoid interacting protein 1, DrosophilaCCAAT-Enhancer-Binding Protein-betaDrosophila ProteinsExcitatory Amino Acid Agentsglutamate receptor IIA, DrosophilaMonomeric Clathrin Assembly ProteinsNerve Tissue ProteinsPeptide FragmentsPICALM protein, humanReceptors, Ionotropic GlutamateTranscription FactorsVesicular Glutamate Transport ProteinsVGlut protein, Drosophila

Identifiers

PMID32592479
PMCPMC7424762
OpenAlexW3037350409

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.