Endocytosis and Alzheimer’s disease
There is growing evidence to link the caveolin proteins involved in non-clathrin-dependent endocytosis to various aspects of AD, as higher levels have been found in AD brains than in non-AD brains. However, attempts to relate the relevance of this finding to the processing of amyloid precursor protein (APP) have produced conflicting results. We have a project funded by BRACE (Bristol Research into Alzheimer’s and Care of the Elderly) which aims to clarify this situation by investigating the hypothesis that the overexpression of caveolins in cells will increase amyloid-β (Aβ) production with potentially deleterious effects in man. The effects of overexpression or knock down of caveolin proteins in cell lines that constitutively express APP will be investigated. It is anticipated that this project will enhance understanding of the role of caveolins in AD and will also provide important information regarding their effects on APP processing and production of Aβ. Currently it is not clear whether the higher levels of Aβ found in AD lead to the observed increases in caveolins or whether increased levels of caveolin represent an earlier causative stage in the disease process. Ultimately, the results should enhance knowledge of the disease process and highlight future therapeutic targets.