Genetic dissection of Alzheimer's disease and related dementias: Amyloid and its relationship to tau

Molecular genetic analysis is revealing the etiologies of Alzheimer's disease (AD) and related dementias. Here we review genetic and molecular biological evidence suggesting that the peptide A beta 42 is central to the etiology of AD. Recent data also suggests that dysfunction in the cytoskeletal protein tau is on the pathway that leads to neurodegeneration and dementia. Tau is produced either indirectly, by A beta 42, or directly, in some forms of frontotemporal dementia by mutations in tau itself. These data support and refine the amyloid cascade hypothesis for AD and suggest that understanding the causes and consquences of tau dysfunction is an important priority for dementia research.