No hippocampal neuron or synaptic bouton loss in learning-impaired aged beta-amyloid precursor protein-null mice

Aged beta-amyloid precursor protein-null mice were used to investigate the relationship between beta-amyloid precursor protein, hippocampal neuron and synaptic bouton number, and cognitive function. Learning and memory perfor mance of aged beta-amyloid precursor protein-null mice and age-matched cont rols were assessed in the Morris water maze. beta-Amyloid precursor protein -null mice demonstrated impaired task acquisition as measured by significan tly longer swim path lengths, a higher percentage of failed trials, and mor e frequent thigmotaxis behavior than controls. In a subsequent probe trial, beta-amyloid precursor protein-null mice spent significantly less time in the old goal quadrant, and made fewer crossings over the old platform locat ion than did controls. No differences in motor or visual skills were observ ed which could account for the performance differences. In light of these f indings and previous evidence for a role of beta-amyloid precursor protein in neuronal maintenance and synaptogenesis, we pursued the hypothesis that the learning impairment of beta-amyloid precursor protein-null mice may be a reflection of differences in neuron or synaptophysin-positive presynaptic bouton number. Thus, unbiased stereological analysis was used to estimate neuron and synaptic bouton number in dentate gyrus and hippocampal CA1 of t he behaviorally characterized mice. No difference in neuron or synaptophysi n-positive presynaptic bouton number was found between the beta-amyloid pre cursor protein-null mice and age-matched controls. Our results suggest that the learning impairment of beta-amyloid precursor protein-null mice is not mediated by a loss of hippocampal neurons or synap tic boutons. (C) 1999 IBRO. Published by Elsevier Science Ltd.