In order to study whether phosphokinases might be involved in the neuropathology of Down Syndrome (DS) and Alzheimer disease (AD), cyclin dependent kinase (CDK) activity and protein, phosphokinase C (PKC) and phosphokinase A (PKA) activities have been determined in frontal lobes of DS, AD and control brains. An enzyme linked immunosorbent assay (ELISA) technique for CDK protein, and commercially available enzyme assays for CDK, PKC and PKA activities have been used. The major finding of our study was the remarkable and significant decrease of CDK protein and activity in DS brains in comparison to AD and controls. PKC and PKA were unaffected in both, AD and DS. As CDK controls cell division and differentiation, lowered CDK levels could reflect impaired proliferation and differentiation in DS.