Exploring Alzheimer's disease in zebrafish

The amyloid-β protein (Aβ)-containing neuritic plaques and hyperphosphorylated tau-containing neurofibrillary tangles are two invariable characteristics of Alzheimer's disease (AD). Three genes encoding amyloid-β protein precursor (AβPP), presenilin (PS) 1 and 2 are linked to early onset familial AD, and the apolipoprotein E (ApoE) ε4 allele is a major risk factor for sporadic AD. The zebrafish AβPP, PS, and ApoE genes have been identified, and the essential components of the γ-secretase complex that mediates cleavage of AβPP to generate Aβ 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 Aβ and tau.