APP(SW) TRANSGENIC MICE DEVELOP AGE-RELATED A-BETA DEPOSITS AND NEUROPIL ABNORMALITIES, BUT NO NEURONAL LOSS IN CA1

The recent availability of transgenic mouse models of Alzheimer diseas e has allowed direct in vivo assessment of the molecular and neuropath ological effects of cerebral amyloid deposition. We examined 16-month- old Tg(HuAPP695. K670N-M671L)2576 mice expressing human APP K670N-M671 L (APP(Sw)), which have amyloid deposition and behavioral deficits by 11 months of age. Transgene expression is predominantly neuronal, and results in amyloid deposits, comparable to human senile plaques, at te rminal zones of transgene positive neurons in cortical and limbic regi ons. Amyloid deposits were associated with prominent gliosis and neuri tic dystrophy, without neuronal loss in CA1, loss of synaptophysin imm unoreactivity in the hippocampal dentate gyrus, or loss of messenger R NA for neuronal synaptic, cytoskeletal, or metabolic proteins. We conc lude that A beta is not acutely neurotoxic, but can disrupt neuronal p rocesses and provoke an inflammatory response.