SPATIAL-LEARNING DEFICIT IN MICE EXPRESSING HUMAN 751-AMINO ACID BETA-AMYLOID PRECURSOR PROTEIN

COGNITIVE and other behavioural characteristics of 3-month-old heteroz ygous male transgenic mice expressing the 751-amino acid isoform of hu man amyloid precursor protein (hAPP(751)) under the control of a neuro ne-specific enolase promoter, were compared with those of age-matched non-transgenic control males. No difference was found between hAPP(751 ) transgenics and non-transgenic controls in passive avoidance learnin g, or in motor coordination. Significantly decreased measures were fou nd in the open field rest and in cage activity indicative of general h ypoactivity in hAPP(751) transgenics. In water maze training, hAPP(751 ) males required significantly longer to locate the hidden platform. T his was not due to decreased swimming velocity in hAPP(751) mice, but rather to increased path lengths. This suggests a purely spatial learn ing deficit in hAPP(751) males even though their performance during a final spatial test, the probe trail that followed water maze was indis tinguishable from that of controls. Decreased activity and impaired sp atial learning were also reported in an independent study of hAPP(751) -expressing transgenics showing beta-amyloid immunoreactive deposits a nd altered tau protein. Since such histopathological alterations were not found in the transgenic model analysed in this study, our results indicate that beta-amyloid deposition is not required for the developm ent of behavioural and/or cognitive deficits in hAPP(751) transgenic m ice.