Relationship of calbindin D28K-immunoreactive cells and neuropathological changes in the hippocampal formation of Alzheimer's disease.

Previous studies have reported that calcium binding proteins, which have important functions in regulating the intracellular ion concentration, may influence the vulnerability of neurons in neurodegenerative disease. It has been observed that the neurons containing calbindin D28K (CB) may in certain circumstances be more resistant to excitotoxic and ischemic injury. In the present study the susceptibility of hippocampal neurons containing CB to develop NFT was studied, and the distribution of CB cells was compared with hippocampal plaque density in the Alzheimer's disease (AD) brain. Interestingly CB-positive hippocampal neurons did not contain tangles and could be seen next to degenerating tau-positive pyramidal cells. Comparison of the hippocampal plaque distribution with that of CB neurons showed that in general CB-positive neurons were found in areas with a low plaque burden. Further comparison of cases with differing degrees of severity indicated that CB-positive neurons were relatively preserved in cases with moderate plaque and tangle content but that in severe cases the CB-positive pyramidal cells were lost. These findings indicate that CB cells may be protected in the earlier stages of the disease but that this resistance ability is lost in the late stages of AD. The observation that CB-positive pyramidal cells do not accumulate NFT suggests that proteolysis of tau differs in CB-negative and CB-positive cells.