Objective. Accumulated evidence has suggested that neurofilament proteins (NFs) are integral components of LB fibrils. High molecular weight (NF-H), middle molecular weight (NF-M), and low molecular weight protein subunits have been identified in LB fibrils. Among these, NF-H and NF-M in LB are abnormally phosphorylated. It has been hypothesized that the phosphorylation of NF proteins is a crucial step for the conversion of NF proteins to the insoluble fibrils of the LB. Recently cdk5, a kinase that is capable of phosphorylating the KSP motif in NF-H and NF-M, was found in LB of PD brains. However, cdk5 needs p35 as a regulatory subunit to be an activative form. If cdk5 is involved in the phosphorylation of NF in LB fibrils, p35 should be associated with LB. Thus, in the present study, we examined the immunohistochemical localization of p35 in PD brains.Methods. Paraffin-embedded sections of postmortem brains from 7 patients with PD and 6 controls were examined. Immunohistochemical staining of p35 were performed using two polyclonal antibodies raised against synthetic peptides corresponding to N-terminal and C-terminal regions of the human p35. Anti-cdk5 antibodies were purchased from Santa-Cruz Biotechnology, Inc, USA.Results. In controls, p35 was immunostained in some neurons and varicose fibers. In PD brains, in addition to neurons and fibers, we found p35-immunoreactive LB in the substantia nigra and locus cereleus. p35-immunoreactivity was mainly observed in the halo of LB. Cdk5 was also immunosatined in LB in accordance with the previous study.Discussion and Conclusion. Cdks are essential molecules for cell-cycle control and 7 types of cdk have been identified. Among these kinases, cdk5 is unique in that mRNA for this kinase has been shown to be relatively abundant in neurons which are post-mitotic. Another unique characteristic is that the protein kinase activity of cdk5 in brain is regulated by a regulatory subunit, p35, which is distinct from cyclins. Members of the cdk family need to associate with cyclins to assume an active form. However, p35 displays no sequence homology to cyclins, and mRNA for p35 is expressed exclusively in the brain. Thus cdk5 has been suggested to be associated with neuronal functions unrelated to the cell cycle in neurons. One of such functions is the ability to phosphorylate KSP motif of C-terminal tail region of NF-M and NF-H, which are major comonents of LB fibrils. In this context, the present results strongly support the hypothesis that cdk5-p35 complex is involved in the formation of LB fibrils in PD.