Calretinin-immunoreactive neurons in the normal human temporal cortex and in Alzheimer's disease

Calretinin-containing neurons (CR) were visualized by immunocytochemistry in the human temporal cortex. The morphology of calretinin-positive neurons ranged from bipolar, bitufted, fusiform to double bouquet cells, whose long axis was parallel to the radial axis of the cortex. Calretinin-immunoreactive cells were more abundant in layers II, III and less frequent in layer VI and white matter. In layer I, large horizontal neurons resembling Cajal-Retzius cells were observed. Layers IV and V contained few labeled cells. The CR-immunoreactive neuropil was abundant, especially in supragranular layers. However, the most prominent feature of the pattern of calretinin staining was the presence of long, vertically oriented bundles of calretinin-immunoreactive processes. These bundles formed a widespread, regular columnar system descending throughout layers II to VI. Despite the virtually identical morphological features of CR-immunoreactive neurons and certain calbindin-immunoreactive neurons, colocalization studies for both antibodies against calretinin and calbindin, revealed little coexistence (in supragranular layers) or none (in infragranular layers). Thus, double bouquet cells could be considered as forming a chemically heterogeneous neuronal population. In addition, four brains from patients with Alzheimer's disease were immunostained for calretinin. No major differences from normal brains were found; the distribution, morphology and the characteristic, vertically oriented bundles resembled those described in normal brains. These data suggest that these calcium-binding protein-containing interneurons are present in normal human brain and that they are resistant to degeneration in Alzheimer's disease.