Evidence map›Paper›PMID 24371804›Full record

ArticleStem cell reports2013

APP processing in human pluripotent stem cell-derived neurons is resistant to NSAID-based γ-secretase modulation.

Jerome Mertens, Kathrin Stüber, Patrick Wunderlich, Julia Ladewig, Jaideep C Kesavan, Rik Vandenberghe, Mathieu Vandenbulcke, Philip van Damme, Jochen Walter, Oliver Brüstle and 1 more

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

Article in Stem cell reports, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
3.1field-weighted citation impact, top 8% 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

37 citing papers in PubMed, 59 citations in OpenAlex.

  1. Review
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  3. Article
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  5. Alzheimer's Disease: Treatment Strategies and Their Limitations.International journal of molecular sciences · 2022
    Review
  6. Article
  7. Emerging hiPSC Models for Drug Discovery in Neurodegenerative Diseases.International journal of molecular sciences · 2021
    Review
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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

11 authors at 4 institutions in 2 countries.

Jerome MertensInstitute of Reconstructive Neurobiology, University of Bonn and Hertie Foundation, 53127 Bonn, Germany.
Kathrin StüberInstitute of Reconstructive Neurobiology, University of Bonn and Hertie Foundation, 53127 Bonn, Germany ; Life&Brain GmbH, 53127 Bonn, Germany.
Patrick WunderlichDepartment of Neurology, University of Bonn, 53127 Bonn, Germany.
Julia LadewigInstitute of Reconstructive Neurobiology, University of Bonn and Hertie Foundation, 53127 Bonn, Germany.
Jaideep C KesavanInstitute of Reconstructive Neurobiology, University of Bonn and Hertie Foundation, 53127 Bonn, Germany.
Rik VandenbergheDepartment of Neurology, University Hospitals Leuven, 3000 Leuven, Belgium ; Laboratory for Cognitive Neurology, Department of Neurosciences, University of Leuven, 3000 Leuven, Belgium.
Mathieu VandenbulckeDepartment of Old Age Psychiatry, University Hospitals Leuven, 3000 Leuven, Belgium.
Philip van DammeDepartment of Neurology, University Hospitals Leuven, 3000 Leuven, Belgium ; Laboratory for Cognitive Neurology, Department of Neurosciences, University of Leuven, 3000 Leuven, Belgium ; Vesalius Research Center, VIB, 3000 Leuven, Belgium.
Jochen WalterDepartment of Neurology, University of Bonn, 53127 Bonn, Germany.
Oliver BrüstleInstitute of Reconstructive Neurobiology, University of Bonn and Hertie Foundation, 53127 Bonn, Germany ; Life&Brain GmbH, 53127 Bonn, Germany.
Philipp KochInstitute of Reconstructive Neurobiology, University of Bonn and Hertie Foundation, 53127 Bonn, Germany ; Life&Brain GmbH, 53127 Bonn, Germany.
University of Bonn · DEHertie Foundation · DEKU Leuven · BELife & Brain (Germany) · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Increasing evidence suggests that elevated Aβ42 fractions in the brain cause Alzheimer's disease (AD). Although γ-secretase modulators (GSMs), including a set of nonsteroidal anti-inflammatory drugs (NSAIDs), were found to lower Aβ42 in various model systems, NSAID-based GSMs proved to be surprisingly inefficient in human clinical trials. Reasoning that the nonhuman and nonneuronal cells typically used in pharmaceutical compound validation might not adequately reflect the drug responses of human neurons, we used human pluripotent stem cell-derived neurons from AD patients and unaffected donors to explore the efficacy of NSAID-based γ-secretase modulation. We found that pharmaceutically relevant concentrations of these GSMs that are clearly efficacious in conventional nonneuronal cell models fail to elicit any effect on Aβ42/Aß40 ratios in human neurons. Our work reveals resistance of human neurons to NSAID-based γ-secretase modulation, highlighting the need to validate compound efficacy directly in the human cell type affected by the respective disease.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesAmyloid Precursor Protein SecretasesAnti-Inflammatory Agents, Non-SteroidalCell DifferentiationCell LineEmbryonic Stem CellsHumansNeuronsPeptide FragmentsPluripotent Stem CellsAmyloid beta-Peptidesamyloid beta-protein (1-42)Amyloid Precursor Protein SecretasesAnti-Inflammatory Agents, Non-SteroidalPeptide Fragments

Identifiers

PMID24371804
PMCPMC3871388
OpenAlexW2085164313

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.