Evidence map›Paper›PMID 32019490›Full record

ArticleBMC neuroscience2020

Proximity ligation assay reveals both pre- and postsynaptic localization of the APP-processing enzymes ADAM10 and BACE1 in rat and human adult brain.

Jolanta L Lundgren, Lina Vandermeulen, Anna Sandebring-Matton, Saheeb Ahmed, Bengt Winblad, Monica Di Luca, Lars O Tjernberg, Elena Marcello, Susanne Frykman

Open access · goldAbstract read
In one paragraph

Article in BMC neuroscience, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
2.3field-weighted citation impact, top 11% 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

15 citing papers in PubMed, 27 citations in OpenAlex.

  1. Article
  2. Non-canonical function of ADAM10 in presynaptic plasticity.Cellular and molecular life sciences : CMLS · 2024
    Article
  3. Article
  4. Article
  5. Novel therapeutic approaches to target neurodegeneration.British journal of pharmacology · 2023
    Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. ADAM10 Plasma and CSF Levels Are Increased in Mild Alzheimer's Disease.International journal of molecular sciences · 2021
    Article
  14. Article
  15. Huntingtin and the Synapse.Frontiers in cellular neuroscience · 2021
    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

9 authors at 3 institutions in 3 countries.

Jolanta L LundgrenDepartment of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Division of Neurogeriatrics, Karolinska Institutet, BioClinicum J9:20, Visionsgatan 4, 171 64, Solna, Sweden.
Lina VandermeulenDepartment of Pharmacological and Biomolecular Sciences, Universitá Degli Studi Di Milano, Milan, Italy.
Anna Sandebring-MattonDepartment of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Division of Neurogeriatrics, Karolinska Institutet, BioClinicum J9:20, Visionsgatan 4, 171 64, Solna, Sweden.
Saheeb AhmedDepartment of Diagnostic and Interventional Radiology, University Medical Center, Göttingen, Germany.
Bengt WinbladDepartment of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Division of Neurogeriatrics, Karolinska Institutet, BioClinicum J9:20, Visionsgatan 4, 171 64, Solna, Sweden.
Monica Di LucaDepartment of Pharmacological and Biomolecular Sciences, Universitá Degli Studi Di Milano, Milan, Italy.
Lars O TjernbergDepartment of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Division of Neurogeriatrics, Karolinska Institutet, BioClinicum J9:20, Visionsgatan 4, 171 64, Solna, Sweden.
Elena MarcelloDepartment of Pharmacological and Biomolecular Sciences, Universitá Degli Studi Di Milano, Milan, Italy.
Susanne FrykmanDepartment of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Division of Neurogeriatrics, Karolinska Institutet, BioClinicum J9:20, Visionsgatan 4, 171 64, Solna, Sweden. susanne.frykman@ki.se.ORCID 0000-0001-6060-1930
Karolinska Institutet · SEUniversity of Milan · ITUniversitätsmedizin Göttingen · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundSynaptic degeneration and accumulation of amyloid β-peptides (Aβ) are hallmarks of the Alzheimer diseased brain. Aβ is synaptotoxic and produced by sequential cleavage of the amyloid precursor protein (APP) by the β-secretase BACE1 and by γ-secretase. If APP is instead cleaved by the α-secretase ADAM10, Aβ will not be generated. Although BACE1 is considered to be a presynaptic protein and ADAM10 has been reported to mainly localize to the postsynaptic density, we have previously shown that both ADAM10 and BACE1 are highly enriched in synaptic vesicles of rat brain and mouse primary hippocampal neurons.

resultsHere, using brightfield proximity ligation assay, we expanded our previous result in primary neurons and investigated the in situ synaptic localization of ADAM10 and BACE1 in rat and human adult brain using both pre- and postsynaptic markers. We found that ADAM10 and BACE1 were in close proximity with both the presynaptic marker synaptophysin and the postsynaptic marker PSD-95. The substrate APP was also detected both pre- and postsynaptically. Subcellular fractionation confirmed that ADAM10 and BACE1 are enriched to a similar degree in synaptic vesicles and as well as in the postsynaptic density.

conclusionsWe show that the α-secretase ADAM10 and the β-secretase BACE1 are located in both the pre- and postsynaptic compartments in intact brain sections. These findings increase our understanding of the regulation of APP processing, thereby facilitating development of more specific treatment strategies.

Indexed as

ADAM10 ProteinAgedAged, 80 and overAmyloid beta-Protein PrecursorAmyloid Precursor Protein SecretasesAnimalsAspartic Acid EndopeptidasesBrainFemaleHumansMaleMembrane ProteinsNeuronsRats, WistarSynapsesSynaptophysinADAM10 ProteinADAM10 protein, humanADAM10 protein, ratAmyloid beta-Protein PrecursorAmyloid Precursor Protein SecretasesAspartic Acid EndopeptidasesBACE1 protein, humanBace1 protein, ratMembrane ProteinsSynaptophysinSYP protein, humanAlzheimer diseaseAmyloid precursor proteinNerve terminalSecretasesSynapse

Identifiers

PMID32019490
PMCPMC7001251
OpenAlexW3004646285

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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.