Chronic elevation of amyloid precursor protein in the neocortex or hippocampus of marmosets with selective cholinergic lesions

In vitro studies have consistently demonstrated a link between cholinergic ne uro transmission and amyloid precursor protein metabolism, although few studies have examined such a relationship in vivo and none have been conduc ted in primate species. The purpose of this study was to test the hypothesi s that a reduction in cholinergic activity in neocortical and hippocampal a reas consequent upon destruction of ascending cholinergic projections may l ead to long-term changes in levels of amyloid precursor protein in these ta rget areas in a primate species. The status of three synaptic proteins asso ciated with neurotransmitter release, synaptophysin, syntaxin and SNAP-25, was also been examined. Selective immunolesions of the basal forebrain chol inergic projections led to increases in amyloid precursor protein-like immu noreactivity in hippocampus and cortex, measured 8 months postlesion. Furth ermore, reductions in cortical and hippocampal SNAP-25, but not syntaxin or synaptophysin, immunoreactivity were observed. These results imply that th e reduced cholinergic activity characteristic of Alzheimer's disease may co ntribute to the continuing emergence of neuropathology in addition to the w ell-known association with cognitive dysfunction.