Introduction and objective: Alzheimer's disease (AD) is a degenerative central nervous system disorder. The histopathologic features include senile plaques, which are composed primarily of insoluble aggregates of amyloid beta-protein (A beta). The purpose of this study was to analyse the effects of A beta on several neurotransmitter/neuromodulator systems as a possible model for the neuropathological changes that occur in AD.
Material and methods: Adult rats (Wistar, 200-300 g) received injections of A beta (12-28) (0.5 microliter-2 microliters, 1 microgram-4 micrograms) into the hypothalamus (mammillary complex) and anterior thalamic nuclei (ATN). After a postinjection survival period of 3 days-3 weeks the rats were perfused and the brains processed for the immunocytochemical localization of several neurochemicals markers.
Results and conclusions: Following injections of A beta into the mammillary nuclei and into ATN a significant decrease in fibres and terminal like-structures immunoreactive for ChAT were found in the cortex and hippocampus. Loss and degeneration of cholinergic neurons was also observed in the basal forebrain (medial septal nucleus, nuclei of the diagonal band of Broca and magnocellular nucleus of Meynert). A similar pattern of changes was also found in the glutamatergic system. Thus, injections of A beta into the mammillary nuclei caused a moderate loss of glutamate-immunoreactive neurons in the ATN and tegmental nuclei of Gudden, whereas injections of A beta into the ATN caused a moderate loss of glutamate-immunoreactive neurons in the retrosplenial cortex, hippocampus and mammillary nuclei. No significant changes were found in the GABAergic system. The alteration of certain neuropeptides, such us the somatostatin, is also a consistent finding. These results indicate the possibility that A beta in vivo caused alteration of different neurotransmitter/neuromodulator markers in the rat brain.