Exploring Alzheimer's Disease in Zebrafish

The amyloid-beta protein (A beta)-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 (A beta PP), presenilin (PS) 1 and 2 are linked to early onset familial AD, and the apolipoprotein E (ApoE) epsilon 4 allele is a major risk factor for sporadic AD. The zebrafish A beta PP, PS, and ApoE genes have been identified, and the essential components of the gamma-secretase complex that mediates cleavage of A beta PP to generate A beta have been examined in zebrafish. A transgenic zebrafish expressing mutant tau has been created, and the transgenic animals exhibit a neurodegeneraton phenotype The use of zebrafish as a model system for AD research has expanded our knowledge of A beta and tau.