Neuropathological study on Abeta toxicity using transgenic mice with human APP

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Amyloid plaques and neurofibrillary tangles are neuropathological and molecular hallmarks for Alzheimer's disease (AD). Their presence is highly important to understand the etiology of the disease. Making model mice is undoubtedly crucial to examine the molecular mechanism how to develop plaque formation and cell death in cerebral tissues and to study a potent therapeutic drug. We tried to make a mouse that bears cerebral amyloid plaques by cross the mutated APP717 (referred to as London mutation) mouse and the mutated PS1 mouse. Both mutations were generated by PCR with human APP and PS1 cDNA templates. These two DNA constructs for transgenic mice were integrated in prion promoter plasmid vector (from Dr. D.Borchelt, Jonhs Hopkins Univ.). We succeeded in generate three lines of mice with human APP717 and two lines of mice with human mutated PS1. The lines were established to show their genetic and protein expression. Amyloid protein was exmained and established to show neurotoxicity using fetal hippocampal neurons derived from these mice. An antagonic effect was found to be associated with crystamine G that is an analogue of congo red to bind amyloid fibril in AD brain.