The older rabbit as an animal model: Implications for Alzheimerʹs disease

Eyeblink classical conditioning (EBCC) is impaired in rabbits and humans during normal aging and severely disrupted in Alzheimerʹs disease (AD) and older Downʹs Syndrome patients (called DS/AD). To determine if older rabbit brains developed neuropathological evidence of Alzheimer-like pathology to account for impaired EBCC, the cerebellum and hippocampus of behaviorally tested rabbits aged 3 months to 7 years were probed using immunohistochemical techniques. Significant cell loss and gliosis were observed in some brain regions, but there was little or no deposition of β-amyloid (Aβ) or abnormal tau accumulations in telencephalic neurons, even in rabbits over 7 years of age. Our aims here are to: 1) report the results of our search for Alzheimer-like neuropathology in aged rabbit brains; and 2) highlight similarities in the brain mechanisms for EBCC between rabbits and humans and, hence, the utility of studies of EBCC in rabbits as a model system for testing cognition-enhancing drugs.