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Endosomal structure and APP biology are not altered in a preclinical mouse cellular model of Down syndrome

Cannavo, C; Cleverley, K; Maduro, C; Mumford, P; Moulding, D; Fisher, EMC; Wiseman, FK; (2022) Endosomal structure and APP biology are not altered in a preclinical mouse cellular model of Down syndrome. PLoS ONE , 17 (5) , Article e0262558. 10.1371/journal.pone.0262558. Green open access

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Abstract

Individuals who have Down syndrome (trisomy 21) are at greatly increased risk of developing Alzheimer’s disease, characterised by the accumulation in the brain of amyloid-β plaques. Amyloid-β is a product of the processing of the amyloid precursor protein, encoded by the APP gene on chromosome 21. In Down syndrome the first site of amyloid-β accumulation is within endosomes, and changes to endosome biology occur early in Alzheimer’s disease. Here, we determine if primary mouse embryonic fibroblasts isolated from a mouse model of Down syndrome can be used to study endosome and APP cell biology. We report that in this cellular model, endosome number, size and APP processing are not altered, likely because APP is not dosage sensitive in the model, despite three copies of App.

Type: Article
Title: Endosomal structure and APP biology are not altered in a preclinical mouse cellular model of Down syndrome
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0262558
Publisher version: https://doi.org/10.1371/journal.pone.0262558
Language: English
Additional information: © 2022 Cannavo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/).
Keywords: Alzheimer Disease, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Animals, Biology, Down Syndrome, Endosomes, Fibroblasts, Mice, Plaque, Amyloid
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > UK Dementia Research Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Biology and Cancer Dept
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
URI: https://discovery.ucl.ac.uk/id/eprint/10149227
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