Evidence map›Paper›PMID 32580751›Full record

ArticleActa neuropathologica communications2020

Ultrastructural and dynamic studies of the endosomal compartment in Down syndrome.

Alexandra Botté, Jeanne Lainé, Laura Xicota, Xavier Heiligenstein, Gaëlle Fontaine, Amal Kasri, Isabelle Rivals, Pollyanna Goh, Orestis Faklaris, Jack-Christophe Cossec and 5 more

Open access · goldAbstract read
In one paragraph

Article in Acta neuropathologica communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
2.7field-weighted citation impact, top 10% 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

30 citing papers in PubMed, 36 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. What Can We Learn About Alzheimer's Disease from People with Down Syndrome?Current topics in behavioral neurosciences · 2025
    Review
  12. Review
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. Article
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

15 authors at 4 institutions in 3 countries.

Alexandra BottéParis Brain Institute (ICM), CNRS UMR7225, INSERM U1127, Sorbonne Université, Hôpital de la Pitié-Salpêtrière, Paris, France.
Jeanne LainéParis Brain Institute (ICM), CNRS UMR7225, INSERM U1127, Sorbonne Université, Hôpital de la Pitié-Salpêtrière, Paris, France.
Laura XicotaParis Brain Institute (ICM), CNRS UMR7225, INSERM U1127, Sorbonne Université, Hôpital de la Pitié-Salpêtrière, Paris, France.
Xavier HeiligensteinCryoCapCell, 155 Bd de l'hôpital, 75013, Paris, France.
Gaëlle FontaineParis Brain Institute (ICM), CNRS UMR7225, INSERM U1127, Sorbonne Université, Hôpital de la Pitié-Salpêtrière, Paris, France.
Amal KasriParis Brain Institute (ICM), CNRS UMR7225, INSERM U1127, Sorbonne Université, Hôpital de la Pitié-Salpêtrière, Paris, France.
Isabelle RivalsEquipe de Statistique Appliquée, ESPCI Paris, PSL Research University, UMRS 1158, Paris, France.
Pollyanna GohThe Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary, University of London, London, UK.
Orestis FaklarisImagoSeine Imaging Core Facility, Institut Jacques Monod, CNRS UMR7592, Université Paris-Diderot, Sorbonne Paris Cité, Paris, France.
Jack-Christophe CossecParis Brain Institute (ICM), CNRS UMR7225, INSERM U1127, Sorbonne Université, Hôpital de la Pitié-Salpêtrière, Paris, France.
Etienne MorelInstitut Necker-Enfants Malades (INEM), INSERM U1151 CNRS UMR 8253, Université Paris Descartes-Sorbonne Paris Cité, Paris, France.
Anne-Sophie RebillatInstitut Jérôme Lejeune, Paris, France.
Dean NizeticThe Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary, University of London, London, UK.
Graça RaposoInstitut Curie, PSL Research University, CNRS, UMR144, Structure and Membrane Compartments, Paris, France.
Marie-Claude PotierParis Brain Institute (ICM), CNRS UMR7225, INSERM U1127, Sorbonne Université, Hôpital de la Pitié-Salpêtrière, Paris, France. marie-claude.potier@upmc.fr.ORCID 0000-0003-2462-7150
Centre National de la Recherche Scientifique · FRQueen Mary University of London · GBAssistance Publique – Hôpitaux de Paris · FRFondation Jérôme-Lejeune · FR

Funding

Wellcome TrustWellcome Trust 098330/Z/12/Z
6 · The paper itself

Abstract

Enlarged early endosomes have been visualized in Alzheimer's disease (AD) and Down syndrome (DS) using conventional confocal microscopy at a resolution corresponding to endosomal size (hundreds of nm). In order to overtake the diffraction limit, we used super-resolution structured illumination microscopy (SR-SIM) and transmission electron microscopies (TEM) to analyze the early endosomal compartment in DS.By immunofluorescence and confocal microscopy, we confirmed that the volume of Early Endosome Antigen 1 (EEA1)-positive puncta was 13-19% larger in fibroblasts and iPSC-derived neurons from individuals with DS, and in basal forebrain cholinergic neurons (BFCN) of the Ts65Dn mice modelling DS. However, EEA1-positive structures imaged by TEM or SR-SIM after chemical fixation had a normal size but appeared clustered. In order to disentangle these discrepancies, we imaged optimally preserved High Pressure Freezing (HPF)-vitrified DS fibroblasts by TEM and found that early endosomes were 75% denser but remained normal-sized.RNA sequencing of DS and euploid fibroblasts revealed a subgroup of differentially-expressed genes related to cargo sorting at multivesicular bodies (MVBs). We thus studied the dynamics of endocytosis, recycling and MVB-dependent degradation in DS fibroblasts. We found no change in endocytosis, increased recycling and delayed degradation, suggesting a "traffic jam" in the endosomal compartment.Finally, we show that the phosphoinositide PI (3) P, involved in early endosome fusion, is decreased in DS fibroblasts, unveiling a new mechanism for endosomal dysfunctions in DS and a target for pharmacotherapy.

Indexed as

AnimalsDown SyndromeEndosomesFibroblastsHumansInduced Pluripotent Stem CellsMiceMicroscopy, ConfocalMicroscopy, Electron, TransmissionTissue FixationVitrificationAlzheimer’s diseaseDown syndromeEarly endosomesElectron microscopyEndocytosisSuper-resolution microscopy

Identifiers

PMID32580751
PMCPMC7315513
OpenAlexW3037082617

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.