Evidence map›Paper›PMID 37443782›Full record

ArticleCells2023

Toward an Early Diagnosis for Alzheimer's Disease Based on the Perinuclear Localization of the ATM Protein.

Elise Berthel, Laurent Pujo-Menjouet, Eymeric Le Reun, Laurène Sonzogni, Joëlle Al-Choboq, Abdennasser Chekroun, Adeline Granzotto, Clément Devic, Mélanie L Ferlazzo, Sandrine Pereira and 2 more

Abstract read
In one paragraph

Article in Cells, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
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

7 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Friends and Foes in Alzheimer's Disease.Medical principles and practice : international journal of the Kuwait University, Health Science Centre · 2023
    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

12 authors.

Elise BerthelInstitut National de la Santé et de la Recherche Médicale, U1296 Research Unit «Radiation: Defense, Health, Environment», Centre Léon-Bérard, 28 Rue Laennec, 69008 Lyon, France.ORCID 0000-0002-7057-1840
Laurent Pujo-MenjouetUniversité Claude-Bernard Lyon 1, CNRS UMR5208, INRIA, Institut Camille-Jordan, 21 Avenue Claude Bernard, 69603 Villeurbanne, France.ORCID 0000-0002-7805-1938
Eymeric Le ReunInstitut National de la Santé et de la Recherche Médicale, U1296 Research Unit «Radiation: Defense, Health, Environment», Centre Léon-Bérard, 28 Rue Laennec, 69008 Lyon, France.
Laurène SonzogniInstitut National de la Santé et de la Recherche Médicale, U1296 Research Unit «Radiation: Defense, Health, Environment», Centre Léon-Bérard, 28 Rue Laennec, 69008 Lyon, France.
Joëlle Al-ChoboqInstitut National de la Santé et de la Recherche Médicale, U1296 Research Unit «Radiation: Defense, Health, Environment», Centre Léon-Bérard, 28 Rue Laennec, 69008 Lyon, France.ORCID 0000-0001-6772-6947
Abdennasser ChekrounUniversité Claude-Bernard Lyon 1, CNRS UMR5208, INRIA, Institut Camille-Jordan, 21 Avenue Claude Bernard, 69603 Villeurbanne, France.
Adeline GranzottoInstitut National de la Santé et de la Recherche Médicale, U1296 Research Unit «Radiation: Defense, Health, Environment», Centre Léon-Bérard, 28 Rue Laennec, 69008 Lyon, France.
Clément DevicInstitut National de la Santé et de la Recherche Médicale, U1296 Research Unit «Radiation: Defense, Health, Environment», Centre Léon-Bérard, 28 Rue Laennec, 69008 Lyon, France.
Mélanie L FerlazzoInstitut National de la Santé et de la Recherche Médicale, U1296 Research Unit «Radiation: Defense, Health, Environment», Centre Léon-Bérard, 28 Rue Laennec, 69008 Lyon, France.
Sandrine PereiraNEOLYS Diagnostics, 7 Allée de l'Europe, 67960 Entzheim, France.ORCID 0000-0003-0807-8323
Michel BourguignonInstitut National de la Santé et de la Recherche Médicale, U1296 Research Unit «Radiation: Defense, Health, Environment», Centre Léon-Bérard, 28 Rue Laennec, 69008 Lyon, France.ORCID 0000-0002-4575-5840
Nicolas ForayInstitut National de la Santé et de la Recherche Médicale, U1296 Research Unit «Radiation: Defense, Health, Environment», Centre Léon-Bérard, 28 Rue Laennec, 69008 Lyon, France.ORCID 0000-0002-1282-1303

Funding

Association Neurofibromatose (ANR) RACKHAM ProjectCentre National d'Études Spatiales ATHENA ProjectCommissariat Général à l'Investissement INDIRA ProjectINSERM transfert TAG-MAAL Project
6 · The paper itself

Abstract

Alzheimer's disease (AD) is the most common neurodegenerative dementia, for which the molecular origins, genetic predisposition and therapeutic approach are still debated. In the 1980s, cells from AD patients were reported to be sensitive to ionizing radiation. In order to examine the molecular basis of this radiosensitivity, the ATM-dependent DNA double-strand breaks (DSB) signaling and repair were investigated by applying an approach based on the radiation-induced ataxia telangiectasia-mutated (ATM) protein nucleoshuttling (RIANS) model. Early after irradiation, all ten AD fibroblast cell lines tested showed impaired DSB recognition and delayed RIANS. AD fibroblasts specifically showed spontaneous perinuclear localization of phosphorylated ATM (pATM) forms. To our knowledge, such observation has never been reported before, and by considering the role of the ATM kinase in the stress response, it may introduce a novel interpretation of accelerated aging. Our data and a mathematical approach through a brand-new model suggest that, in response to a progressive and cumulative stress, cytoplasmic ATM monomers phosphorylate the APOE protein (pAPOE) close to the nuclear membrane and aggregate around the nucleus, preventing their entry in the nucleus and thus the recognition and repair of spontaneous DSB, which contributes to the aging process. Our findings suggest that pATM and/or pAPOE may serve as biomarkers for an early reliable diagnosis of AD on any fibroblast sample.

Indexed as

Alzheimer DiseaseDNA RepairAtaxia Telangiectasia Mutated ProteinsCell NucleusDNA Breaks, Double-StrandedHumansAtaxia Telangiectasia Mutated ProteinsATM protein, humanagingAlzheimer’s diseaseAPOEATMDNA double-strand breaksfibroblastsimmunofluorescenceirradiation

Identifiers

PMID37443782
PMCPMC10340316

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.