Loss of calbindin-D28K from aging human cholinergic basal forebrain: relation to plaques and tangles.

Reports from our laboratory have indicated a substantial and specific loss of the calcium binding protein calbindin-D28K (CB) from the human basal forebrain cholinergic neurons (BFCN) in the course of normal aging. In the present set of experiments we determined the relationship between the age-related loss of CB and the presence and density of plaques and tangles in the brains of normal elderly. In 23 cases ranging in age from 20 to 93 years of age we observed plaques and tangles in the BFCN region and the cerebral cortex in a subset of cases. Plaques were seen in the basal forebrain in very few cases above 65 years. Plaque density in the basal forebrain and cortex displayed a significant negative correlation with the proportion of the BFCN, which contained CB immunoreactivity. However, the brains of 2 elderly cases that displayed a substantial loss of CB from the BFCN did not contain any plaques. Tangles were observed in the BFCN as early as 26 years of age. Only tangles in the entorhinal cortex showed a significant negative correlation with the loss of CB from the BFCN. It is likely that loss of CB from the BFCN and formation of plaques and tangles are part of general age-related processes that occur in parallel rather than being causally related.