ACCUMULATION OF CYCLIN-DEPENDENT KINASE-5 (CDK5) IN NEURONS WITH EARLY STAGES OF ALZHEIMERS-DISEASE NEUROFIBRILLARY DEGENERATION

Cyclin-dependent kinase 5 (cdk5) is one of the candidate kinases invol ved in the abnormal hyperphosphorylation. of tau. To have a direct eff ect on tau hyperphosphorylation, cdk5 protein levels and enzyme activi ty should be upregulated in especially those neurons that develop neur ofibrillary tangles (NFTs). We studied the distribution of cdk5 immuno reactivity in neurons with or without early- and late-stage NFTs in hi ppocampal, entorhinal, transentorhinal, temporal and frontal cortices, and cerebellum of Alzheimer's disease (AD) and control brain. The imm unocytochemical localisation of cdk5 vias compared with that obtained using antibodies to PHF-tau (tau in paired helical filaments of NFTs, mAb AT8) and ubiquitin as markers of early and late stage NFTs, respec tively. Immunoreactivities of cdk5 and PHF-tau were found in neuronal perikarya and processes of hippocampal, entorhinal, transentorhinal, t emporal and frontal, and cerebellar cortices. An apparent increase of cdk5 immunoreactivity was seen in pretangle neurons and in neurons bea ring early stage NFTs. These findings suggest that this kinase might b e involved in the formation of NFTs at a relatively early stage in the neocortex. (C) 1998 Elsevier Science B.V. All rights reserved.