AGE-RELATED CNS DISORDER AND EARLY DEATH IN TRANSGENIC FVB N MICE OVEREXPRESSING ALZHEIMER AMYLOID PRECURSOR PROTEINS/

Transgenic FVB/N mice overexpressing human (Hu) or mouse (Mo) Alzheime r amyloid precursor protein (APP(695)) die early and develop a CNS dis order that includes neophobia and impaired spatial alternation, with d iminished glucose utilization and astrogliosis mainly in the cerebrum. Age at onset of neophobia and age at death decrease with increasing l evers of brain APP. HuAPP transgenes induce death much earlier than Mo APP transgenes expressed at similar levels. Na extracellular amyloid w as detected, indicating that some deleterious processes related to APP overexpression are dissociated from formation of amyloid. A similar c linical syndrome occurs spontaneously in similar to 20% of nontransgen ic mice when they reach mid- to late-adult life, suggesting that APP o verexpression may accelerate a naturally occuring age-related CNS diso rder in FVB/N mice.