TRANSGENIC MICE EXPRESSING AN ALPHA-SECRETION MUTANT OF THE AMYLOID PRECURSOR PROTEIN IN THE BRAIN DEVELOP A PROGRESSIVE CNS DISORDER

Expression of alpha-secretion mutant APP/RK in mouse brain results in a progressive disorganization of the central nervous system, exemplifi ed by behavioral deficits, premature death and neuropathology. Here we report on the progressive nature of this CNS disorder as indicated by the age dependency of the neophobic reaction in the open-field test. The earlier reported NMDA hypo-sensitivity in the transgenic APP/RK mi ce is likely to represent a subtle functional disturbance, since no ch anges in NMDA receptor density or distribution could be detected. None of the typical neuropathological hallmarks of Alzheimer's Disease, i. e. amyloid deposits and neurofibrillary tangles are detected in the br ain of these transgenic mice. Nevertheless, the progressive CNS disord er elicited in the transgenic APP/RK mice recapitulates certain featur es and symptoms of patients with Alzheimer's disease as discussed. (C) 1998 Elsevier Science B.V. All rights reserved.