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 are refine the amyloid cascade hypothesis for AD and suggest that understanding the causes and consequences of tau dysfunction is an important priority for dementia research.
Hardy
J
J
Neurogenetics and Transgenics Laboratories, Mayo Clinic Jacksonville, Florida 32224, USA. hardy.john@mayo.edu
Duff
K
K
Hardy
K G
KG
Perez-Tur
J
J
Hutton
M
M
D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000502:physiology; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D003704:Dementia / Q000235:genetics* / Q000473:pathology; D006801:Humans; D009154:Mutation / Q000502:physiology; D009410:Nerve Degeneration / Q000209:etiology; D010300:Parkinson Disease / Q000235:genetics; D010446:Peptide Fragments / Q000502:physiology; D058225:Plaque, Amyloid / Q000502:physiology; D016875:tau Proteins / Q000235:genetics / Q000502:physiology
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins