HIPPOCAMPAL BETA-AMYLOID REDUCES LOCUS-COERULEUS GLUTAMATE AND TYROSINE-HYDROXYLASE

The effects of intrahippocampally injected beta-amyloid protein (beta- AP) on glutamate- (Glu) and tyrosine hydroxylase (TH)-like immunoreact ivities in the neurons of the locus coeruleus (LC) were studied in rat s. A synthetic peptide or the vehicle alone was injected into the hipp ocampus as controls. All injections were made once a week (two or thre e injections; 3 nmol in 2 mu l of distilled water). Fluorescent micros pheres (either alone or with one of the peptides) were also injected i nto the hippocampus to identify coeruleohippocampal neurons. The resul ts revealed cell loss in the hippocampus at the site near beta-AP or c ontrol peptide deposition. Furthermore, in beta-AP/microsphere injecte d animals, only 22.4% and 49.6% of hippocampal projection neurons cont ained Glu and TH, respectively, compared to 88.4% and 85.3% in the ani mals that received control peptide with microspheres. Our results sugg est that beta-AP has an effect on noradrenergic cells whose axons proj ect to the hippocampus. These effects may contribute to the TH cell lo ss in the LC of Alzheimer's brains.