We have previously isolated from the hippocampus of young rats a novel
peptide termed '
hippocampal cholinergic neurostimulating peptide' (
HCNP) which specifically enhances the
cholinergic activity of the septohippocampal 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
protein. An affinity-purified rabbit antibody to rat
HCNP prepared by us recognizes the C-terminal domain of the
peptide, while an antibody against human
HCNP binds to a large portion of the
peptide. In this report we show that both
antibodies react with
HCNP-related components present in the soluble cytosol fraction of human brain tissue. Immunohistochemical examination of human nervous system tissues from elderly individuals revealed that Hirano bodies in Sommer's sector of the hippocampus 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 immunohistochemical results were substantiated by immunoelectron microscopy. The present 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.