Alzheimer's disease research on brain organoids
2021
Ruhr University Bochum, Bochum, Germany
The amyloid precursor protein (APP) is a type I transmembrane protein with an unknown physiological function but a potential impact on neurodegeneration. The current study demonstrates that APP is involved in nuclear signalling causing the generation of aggregates consisting of its adapter protein FE65, the histone acetyltransferase TIP60 and the tumour suppressor proteins p53 and PML. APP C-terminal (APP-CT50) complexes co-localize and co-precipitate with p53 and PML. The PML nuclear body generation is induced and fusion occurs over time depending on APP signalling and STED (Stimulated Emission Depletion) imaging revealed active gene expression within the complex. It could be shown that the nuclear aggregates of APP-CT50 fragments together with PML and FE65 are present in the aged human brain but not in cerebral organoids differentiated from iPS cells. Notably, human Alzheimer’s disease (AD) brains reveal a highly significant reduction of these nuclear aggregates in areas with high plaque load compared to plaque-free areas of the same individual. Based on these results, it can be concluded that APP-CT50 nuclear signalling takes place in the aged human brain and is involved in the pathophysiology of AD.
Amyloid precursor protein elevates fusion of promyelocytic leukemia nuclear bodies in human hippocampal areas with high plaque load
Thorsten Müller
Added on: 05-12-2021
[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042982/
