AGE-RELATED LEARNING-DEFICITS IN TRANSGENIC MICE EXPRESSING THE 751-AMINO ACID ISOFORM OF HUMAN BETA-AMYLOID PRECURSOR PROTEIN

The beta-amyloid precursor protein (beta-APP), from which the beta-A4 peptide is derived, is considered to be central to the pathogenesis of Alzheimer disease (AD), Transgenic mice expressing the 751-amino acid isoform of human beta-APP (beta.APP(751)) have been shown to develop early AD-like histopathology with diffuse deposits of beta.A4 and aber rant tau protein expression in the brain, particularly in the hippocam pus, cortex, and amygdala. We now report that beta.APP(751) transgenic mice exhibit age-dependent deficits in spatial learning in a water-ma ze task and in spontaneous alternation in a Y maze. These deficits wer e mild or absent in 6-month-old transgenic mice but were severe in 12- month-old transgenic mice compared to age-matched wild-type control mi ce. No other behavioral abnormalities were observed, These mice theref ore model the progressive learning and memory impairment that is a car dinal feature of AD. These results provide evidence for a relationship between abnormal expression of beta-APP and cognitive impairments.