Effects of wild-type and mutant human amyloid precursor protein on cortical afferent network

Alzheimer's disease is characterized by severe neuronal disintegration supposed to be partly associated with amyloid pathology. Recently, we described morphological alterations of pyramidal cell structure in transgenic mice expressing wild-type or mutant human amyloid precursor protein (hAPP) (strains B6-Py8.9 and Tg2576), which are unrelated to direct plaque-associated changes. In this study, we focused on the pattern of cortical afferent connections in these transgenic mice. The quantity of cholinergic afferents is increased in both transgenic lines. Glutamatergic intra- and interhemispheric afferents are augmented in B6-Py8.9 mice but decreased in Tg2576 mice. Furthermore, perisomatic inhibition of pyramidal neurons was found to be reduced in Tg2576 mice. Findings suggest different effects of wild-type and mutant hAPP on neuronal connectivity.