Chromogranin A-like immunoreactive neurites are major constituents of senile plaques

The distribution of chromogranin A (CgA), a soluble protein in dense-core synaptic vesicles expressed by a variety of neuronal cell types, was studied immunocytochemically in Alzheimer's disease and normal aging. In addition to its presence in neuronal perikarya and process, CgA-like immunoreactivity (CgA-li) was demonstrated in multiple dystrophic neurites forming the crown of senile plaques. Two different monoclonal antibodies, LK2H10 and PHE5, gave identical results. In the two regions of the brain studied--the calcarine cortex and the molecular layer of the dentate gyrus--the areal density of plaques associated with CgA-like immunoreactive neurites was greater than the density of Congo red-stainable amyloid cores, but smaller than the density of beta amyloid peptide deposits identified by the Campbell silver stain. By comparison, other synaptically released peptides--somatostatin 28, somatostatin 14, substance P, cholecystokinin, neurotensin, vasoactive intestinal peptide, and leu-enkephalin--were immunocytochemically detected in less than 30% of plaques. Thus CgA appears unique among known synaptically released substances in being present in dystrophic neurites in virtually all classic (i.e., Congo red stainable) plaques and additionally in a subpopulation of preamyloid plaques.