ABNORMAL EXPRESSION OF THE CELL-CYCLE REGULATORS P16 AND CDK4 IN ALZHEIMERS-DISEASE

In this study, we demonstrate that two important regulators of the cel l cycle, cyclin-dependent kinase-4 and its inhibitor p16, are increase d in the brains of cases of Alzheimer's disease patients compared with age-matched controls. Both proteins are increased in the pyramidal ne urons of the hippocampus, including those neurons containing neurofibr illary tangles and granulovacuolar degeneration. As p16 is not normall y found in terminally differentiated neurons, it seems paradoxical tha t it is increased in Alzheimer's disease unless it is responding to in creases in cyclin-dependent kinase-4 or other cell cycle regulators. I nduction of the latter, a protein that signals re-entry and progressio n through the cell cycle, may itself be the consequence of a response to a growth stimulus. Re-entry into the cell cycle is likely deleterio us in terminally differentiated neurons and may contribute to the bioc hemical abnormalities, such as oxidative stress and hyperphosphorylate d tau protein, as well as the neuronal degeneration characteristic of the pathology of Alzheimer's disease.