ACCUMULATION OF HIPPOCAMPAL CHOLINERGIC NEUROSTIMULATING PEPTIDE (HCNP)-RELATED COMPONENTS IN HIRANO BODIES

We have previously isolated from the hippocampus of young rats a novel peptide termed 'hippocampal cholinergic neurostimulating peptide' (HC NP) which specifically enhances the cholinergic activity of the septoh ippocampal system in vitro, Cloning and base sequence analysis of HCNP -specific cDNA from rat and human cDNA libraries revealed that the 1.1 kDa peptide aligns at the N-terminal region of its 21 kDa precursor p rotein. An affinity-purified rabbit antibody to rat HCNP prepared by u s recognizes the C-terminal domain of the peptide, while an antibody a gainst human HCNP binds to a large portion of the peptide. In this rep ort we show that both antibodies react with HCNP-related components pr esent in the soluble cytosol fraction of human brain tissue. Immunohis tochemical examination of human nervous system tissues from elderly in dividuals revealed that Hirano bodies in Sommer's sector of the hippoc ampus were specifically stained by anti-HCNP antibodies. The number of HCNP-positive Hirano bodies was greater in patients with Alzheimer's disease than in normal, age-matched individuals. The immunohistochemic al results were substantiated by immunoelectron microscopy. The presen t findings indicate that HCNP-related components accumulate in Hirano bodies, suggesting that patients who bear these inclusions may have a disturbance of the septo-hippocampal cholinergic system, considered to be of importance for learning and memory formation.