Secretoneurin is a recently described peptide derived by endoproteolytic processing from secretogranin II, previously named chromogranin C. In this study, we have investigated the distribution of secretoneurin‐like immunoreactivity in the human hippocampus in controls and in Alzheimer's disease patients, and compared the staining pattern to that of calretinin. Secretoneurin‐like immunoreactivity is present throughout the hippocampal formation. At the border of the dentate molecular layer and the granule cell layer, a band of dense secretoneurin immunostaining appeared. In this part, as in the area of the CA2 sector, the high density of secretoneurin‐immunoreactivity coincided with calretinin‐like immunoreactivity. The mossy fibre system displayed a moderate density of secretoneurin‐immunoreactivity. In the entorhinal cortex, a particularly high density of secretoneurin‐immunoreactivity was observed. The density of secretoneurin‐like immunoreactivity was significantly reduced in the innermost part of the molecular layer and in the outer molecular layer of the dentate gyrus in Alzheimer's disease. For calretinin‐like immunoreactivity, a less pronounced decrease was found in the innermost part of the molecular layer. About 40–60% of neuritic plaques were secretoneurin‐immunopositive.

This study shows that secretoneurin is distinctly distributed in the human hippocampus and that significant changes of secretoneurin‐like immunoreactivity occur in Alzheimer's disease, reflecting synaptic loss.