Alzheimer's disease(AD)is the most common neurodegenerative disease without effective treatment.?-amyloid peptide(A?)has been proposed to be causally associated with AD.Ap is generated by sequential enzymatic processing of amyloid precursor protein(APP),a type I membrane protein with an exceptionally large N-terminal extracellular domain.However,it remains elusive whether and how the N-terminal domain regulates the processing of APP and the generation of A?.In this thesis,we have examined the effects of the N-terminal domains on the processing of APP.We have made a serise of APP mutants with truncations in its N-terminus.By comparing the processing products of these truncation mutants,we have identified two domains,i.e.ACIDIC and CAPPD,that may play essential roles in regulating A? production.Further investigations are warranted to identify the underlying mechanisms. |