Oxidative modification of creatine kinase BB in Alzheimer's disease brain

Creatine kinase (CK) BB, a member of the CK gene family, is a predominantly cytosolic CK isoform in the brain and plays a key role in regulation of th e ATP level in neural cells. CK BB levels are reduced in brain regions affe cted by neurodegeneration in Alzheimer's disease (AD), Pick's disease, and Lewy body dementia, and this reduction is not a result of decreased mRNA le vels. This study demonstrates that posttranslational modification of CK BB plays a role in the decrease of CK activity in AD brain. The specific CK BB activity and protein carbonyl content were determined in brain extracts of six AD and six age-matched control subjects. CK BB activity per microgram of immunoreactive CK BB protein was lower in AD than in control brain extra cts, indicating the presence of inactive CK BB molecules. The analysis of s pecific protein carbonyl levels in CK BB, performed by two-dimensional fing erprinting of oxidatively modified proteins, identified CK BB as one of the targets of protein oxidation in the AD brain. The increase of protein carb onyl content in CK BB provides evidence that oxidative posttranslational mo dification of CK BB plays a role in the loss of CK BB activity in AD.