Alzheimer's disease, model systems and experimental therapeutics

Abstract

This chapter focuses on important research relevant to Alzheimer's disease (AD) including: the diagnosis of clinical syndrome; value of laboratory studies, particularly new imaging efforts; and advances in genetics and neuropathology/biochemistry. It discusses the pathogenesis of AD and development of experimental models of value for understanding disease mechanisms and for developing experimental therapeutics. Transgenic approaches have been used to model features of autosomal dominant neurodegenerative diseases in mice. In mice, expression of APPswe or APP717 minigenes leads to an Aβ amyloidosis in the murine central nervous system (CNS). To better understand the functions of some of the proteins playing roles in AD, investigators have targeted genes encoding these proteins, including: APP; amyloid precursor-like protein genes (APLPs); BACE1; PS1; Nct; and Aph-1. Both β and γ-secretase activities represent therapeutic targets for the development of novel protease inhibitors.