CORTICAL AND BRAIN-STEM-TYPE LEWY BODIES ARE IMMUNOREACTIVE FOR THE CYCLIN-DEPENDENT KINASE-5

The immunoreactivity of cortical and brainstem-type Lewy bodies has be en investigated with antibodies to the cyclin-dependent kinase 5 (cdk5 ), to the extracellular regulated kinase 1 (ERK-1), and to the cdc2p34 kinase and with antibodies specific for phosphorylation epitopes typi cal of paired helical filament-tau (PHF-tau). Both cortical and brains tem-type Lewy bodies in diffuse Lewy body disease and brainstem-type L ewy bodies in Parkinson's disease were found to be immunoreactive for cdk5 but not for cdc2p34 or ERK-1 or with the PHF-tau antibodies. Doub le immunolabeling showed that cdk5-positive Lewy bodies were also ubiq uitin immunoreactive and that cdk5 antibodies labeled as many Lewy bod ies as ubiquitin antibodies in adequately fixed tissue. The cdk5 immun oreactivity of Lewy bodies with a cdk5 peptide. The antibodies to cdk5 labeled a single 33-kd species on Western blots of human brain homoge nates, with a similar intensity in control, diffuse Lewy body disease, and Alzheimers's disease, and this cdk5 species was found mainly in t he particulate fraction of brain homogenates. This observation suggest s that cdk5 might be a protein kinase involved in the phosphorylation of a molecular component of Lewy bodies, for example, neurofilament pr oteins known to be present in these inclusions.