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

• Published in: PloS one Vol. 17; no. 5; p. e0262558
• Main Authors: Cannavo, Claudia, Cleverley, Karen, Maduro, Cheryl, Mumford, Paige, Moulding, Dale, Fisher, Elizabeth M. C., Wiseman, Frances K.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 11.05.2022; Public Library of Science (PLoS)
• Subjects: Accumulation; Alzheimer Disease - genetics; Alzheimer Disease - metabolism; Alzheimer's disease; Alzheimers disease; Amyloid beta-Peptides - metabolism; Amyloid beta-Protein Precursor - genetics; Amyloid beta-Protein Precursor - metabolism; Amyloid precursor protein; Analysis; Animals; Biology; Biology and Life Sciences; Cells; Chromosome 21; Computer and Information Sciences; Diagnosis; Down syndrome; Down Syndrome - genetics; Down Syndrome - metabolism; Down's syndrome; Embryo fibroblasts; Endosomes; Endosomes - metabolism; Engineering and Technology; Fibroblasts; Fibroblasts - metabolism; Genes; Genetic aspects; Medicine and Health Sciences; Mice; Modelling; Neurodegenerative diseases; Plaque, Amyloid - metabolism; Proteins; Research and Analysis Methods; Senile plaques; Trisomy; β-Amyloid; United Kingdom
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0262558

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 .