Comparison of Ca(2+)-activated proteinase enzyme and endogenous inhibitor activity in brain tissue from normal and Alzheimer's disease cases.

Recent evidence has suggested that Alzheimer's disease may result from an underlying defect of protein catabolism. In an attempt to identify such a defect, we have determined the levels of Ca(2+)-activated proteinase (principally calpain II) and endogenous inhibitor (calpastatin) activity in normal and Alzheimer's disease cases, following fractionation of parietal cortex (grey and white matter) via anion-exchange chromatography. The chromatographic elution profiles and levels of calpain II activity were found to be similar in grey and white matter in both normal and Alzheimer's disease cases. The characteristics of calpain II, including Ca2+ concentration required for optimum activity for enzymes partially purified from normal or Alzheimer's disease cortex were identical. Similarly, the chromatographic elution profiles and levels of total calpastatin activity (approximately equal to that for calpain II activity) were found to be similar in grey and white matter from normal and Alzheimer's disease cases. These data suggest that the characteristic neurodegeneration associated with Alzheimer's disease does not result from alteration in the level of activity or characteristics of the calpain/calpastatin system in the cerebral cortex of patients with this disorder.