Transgenic animals in Alzheimer's disease research.
Alzheimer's disease (AD) is a neurodegenerative disorder of the brain accounting for about 50-70% of the typical late onset cases of dementia. The pathological and diagnostic hallmarks of the disease are principally the presence of extracellular deposits called neuritic amyloid plaques and the intracellular aggregation of neurofibrillary tangles. In addition selective neuronal cell loss accompanied by cerebrovascular amyloidosis is detectable. In the case of familial AD, defects in at least three different genes (APP, PS1, PS2) leading to indistinguishable pathology are now well defined. There is as yet no real treatment for AD. Therefore the availability of an easily manipulable animal model is crucial for the development of new drugs, which could slow down or, even better, stop the progression of the disease. The development and originality of such experimental models that could greatly facilitate the investigation of the aetiology and pathogenesis of AD are described and discussed in this review. They are based mainly on the attempt to reproduce the neurofibrillary tangles or the amyloid deposits and plaque formation.
Sturchler-Pierrat
C
C
Novartis Pharma Inc., Nervous System Research, Basel, Switzerland.
Sommer
B
B
D000544:Alzheimer Disease / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D008822:Mice, Transgenic / Q000235:genetics; D009154:Mutation; D016874:Neurofibrillary Tangles / Q000235:genetics* / Q000378:metabolism; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D058225:Plaque, Amyloid / Q000235:genetics* / Q000378:metabolism
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D001057:Apolipoproteins E; D008565:Membrane Proteins; D010446:Peptide Fragments