APP and Down syndrome: Directly inhibiting APP expression has been shown to revert phenotypic abnormalities both in vitro (endosomal abnormality in Down’s syndrome fibroblasts and rate of apoptosis in cortical and hippocampal neurons from APP transgenic mice) [119,120] and in vivo (behavioural phenotype in mice over expressing APP or mutant APP) [56,121], which has encouraged further investigation of RNAi in relation to AD.