Ontogenetic expression of spot 35 protein (calbindin-D28k) in human olfactory receptor neurons and its decrease in Alzheimer's disease patients

Expression of a calcium-binding protein, spot 35 protein (S-35, calbindin-D28k), was investigated immunohistochemically in the human olfactory mucosa of patients who ranged in age from 16 weeks of fetal development to 98 years old, including some with Alzheimer's disease (AD). S-35 immunoreactivity was observed clearly in olfactory receptor neurons (ORNs) and olfactory nerve bundles that were identified previously with antibodies to olfactory marker protein (OMP) and neuron-specific enolase (NSE). Throughout all ages, the mean number of ORNs immunoreactive for OMP did not change significantly, whereas the mean number of NSE- and S-35-immunoreactive ORNs declined markedly in the postnatal infant, young, and old patients when compared with that of the prenatal fetuses. S-35-immunoreactive ORNs decreased significantly in AD patients when compared with AD control patients. These results indicate that ORNs in humans express S-35 and that there is an age-related trend in the expression of S-35. Furthermore, the marked decrease of S-35 expression in ORNs of AD patients suggests that cell excitability associated with calcium ions and cell protective function against overload of intracellular calcium ions decline in these patients.