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.
Xia
Weiming
W
Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. wxia@rics.bwh.harvard.edu
D000544:Alzheimer Disease / Q000473:pathology*; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000235:genetics; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D030801:Animals, Genetically Modified; D001057:Apolipoproteins E / Q000235:genetics; D006801:Humans; D053764:Presenilin-1 / Q000235:genetics; D053766:Presenilin-2 / Q000235:genetics; D051880:Receptors, Notch / Q000378:metabolism; D015027:Zebrafish / Q000502:physiology*; D029961:Zebrafish Proteins / Q000235:genetics; D016875:tau Proteins / Q000235:genetics
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D001057:Apolipoproteins E; D053764:Presenilin-1; D053766:Presenilin-2; C543887:Psen1 protein, zebrafish; C543888:Psen2 protein, zebrafish; D051880:Receptors, Notch; D029961:Zebrafish Proteins; D016875:tau Proteins; D053829:Amyloid Precursor Protein Secretases