1B)
1B). characterized by the progressive cerebral accumulation of amyloid- (A) deposits in either dense-core senile plaques or diffuse amorphous plaques (1). In vivo imaging studies strongly support the amyloid hypothesis, which postulates that formation of senile plaques initiates a pathological cascade resulting in recruitment of microglia and induction of local neuritic changes near the plaques (2,3). A is composed primarily of 40- and 42-amino acid peptides generated from the amyloid precursor protein (APP) by sequential proteolytic cleavages mediated by - and -secretases (4). Many anti-amyloid therapies are currently in development but only a few have successfully reversed existing amyloid pathology (2,5). In regulatable APP transgenic mice, a conceptual model for therapies targeting A generation, plaque pathology could not be reversed by simply shutting down APP over-expression and A production (6).…