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

Autor: Cannavo C; UK Dementia Research Institute, UCL Queen Square Institute of Neurology, London, United Kingdom.; Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, United Kingdom., Cleverley K; Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, United Kingdom., Maduro C; Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, United Kingdom., Mumford P; UK Dementia Research Institute, UCL Queen Square Institute of Neurology, London, United Kingdom., Moulding D; Light Microscopy Core Facility, UCL Great Ormond Street Institute of Child Health, London, United Kingdom., Fisher EMC; Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, United Kingdom., Wiseman FK; UK Dementia Research Institute, UCL Queen Square Institute of Neurology, London, United Kingdom.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2022 May 11; Vol. 17 (5), pp. e0262558. Date of Electronic Publication: 2022 May 11 (Print Publication: 2022).
DOI: 10.1371/journal.pone.0262558
Abstrakt: 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.
Competing Interests: F.K.W. has undertaken consultancy for Elkington and Fife Patent Lawyers unrelated to the work in the manuscript and is also a PLoS ONE Academic Editor. This does not alter our adherence to PLoS ONE policies on sharing data or materials
Databáze: MEDLINE