Exploring Alzheimer's disease in zebrafish.

The amyloid-beta protein (Abeta)-containing neuritic plaques and hyperphosphorylated tau-containing neurofibrillary tangles are two invariable characteristics of Alzheimer's disease (AD). Three genes encoding amyloid-beta protein precursor (AbetaPP), presenilin (PS) 1 and 2 are linked to early onset familial AD, and the apolipoprotein E (ApoE) epsilon4 allele is a major risk factor for sporadic AD. The zebrafish AbetaPP, PS, and ApoE genes have been identified, and the essential components of the gamma-secretase complex that mediates cleavage of AbetaPP to generate Abeta have been examined in zebrafish. A transgenic zebrafish expressing mutant tau has been created, and the transgenic animals exhibit a neurodegeneration phenotype. The use of zebrafish as a model system for AD research has expanded our knowledge of Abeta and tau.