Immunohistochemical Characterization of Alzheimer in Transgenic Mice Carrying Both Mutant Amyloid Precursor Protein and Presenilin 1 Transgenes: Focus on Neuronal Death in the Basal Forebrain
Newly developed doubly transgenic mice expressing mutant forms of the amyloid precursor protein and presenilin-1 genes, demonstrate elevated levels of Ab42 relative to singly transgenic and nontransgenic littermates at the same age. These doubly transgenic mice develop fibrillar Ab deposits exclusively in the cerebral cortex and hippocampus, with large numbers visible by 29 weeks of age. These results indicate that the effects of presenilin and APP mutations of Ab42 levels are additive and the elevated Ab42 levels lead to accelerated Ab deposition. In addition, the doubly transgenic mice also exhibit neuronal loss in the nucleus basalis of Meynert. The combination of these two results help to solidify the importance of this transgenic model. It can now serve as a vehicle by which at least two pathological features of human Alzheimer's disease can be mimicked and studied. Ultimately, this transgenic model will help in determining the cascade by which amyloid is deposited in AD, and reveal possible areas for drug treatment.
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