Alteration of cholinergic, excitatory amino acid and neuropeptide markers in the septum-diagonal band complex following injections of fibrillar ß-amyloid protein into the retrosplenial granular cortex of the rat.

The effects on cholinergic, excitatory amino acid and neuropeptide markers in the basal forebrain of an intracerebrally-injected synthetic peptide corresponding to the first 1-40 amino acids of beta-amyloid protein (Ab1-40) was studied in rats. Focal deposition of Ab in the retrosplenial granular cortex resulted in a significant loss of cholinergic and glutamate-immunoreactive neurons in the septum-diagonal band complex. The medial septal nucleus showed a reduction of 39% ± 1% in the number of cholinergic neurons and a significantly reduced number of cholinergic neurons (up to 22% ± 10%) was also found in the horizontal nucleus of the diagonal band of Broca in comparison with the same paramaters in uninjected controls. A markerd loss of glutamate- containing neurons was also found in the medial septal nucleus (up to 19% ± 6%) together with a decrease of approximately 22% ± 3% in the horizontal nucleus of the diagonal band of Broca when compared with uninjected control animals. Furthermore, a moderate reduction in fibres and structures such as terminals immunoreactive for glutamate, substance P, and neurotensin was observed in the septum-diagonal band complex. These results show that two different neurochemically defined populations of neurons in the basal forebrain are affected by the neurotoxicity of Ab in vivo