Extraordinary progress has been made in understanding the neuronal populations at risk in AD and some of the mechanisms of cytoskeletal pathology; however, most recent research has focused on the mechanisms of amyloidogenesis and the processing of APP and A beta in in vitro and in vivo systems, including aged nonhuman primates and transgenic mice. Over the next several years, we anticipate that transgenic mice recapitulating many of the features of AD will be produced and that these animals will be very useful for defining the etiologies of this disease, for delineating mechanisms of cell dysfunction and death, and for testing novel therapies. Finally, because several other genetic risk factors, including apoE and chromosome 19 and a locus on chromosome 14, have been identified, it is anticipated that future studies will focus on the role of the products of these genes on the cytoskeleton and APP processing, which will represent exciting and challenging new areas of research.