Cyclin-dependent kinase 5 colocalizes with phosphorylated tau in human inclusion-body myositis paired-helical filaments and may play a role in tau phosphorylation

To investigate the possible role of cyclin-dependent kinase 5 (cdk5) in the formation of paired helical filaments (PHFs) in muscle of patients with inclusion-body myositis (IBM), we immunolocalized cdk5, by light- and electron-microscopy, in muscle biopsies of six IBM patients. Approximately 80-90% of IBM vacuolated muscle fibers, and 10-15% of non-vacuolated fibers, contained well defined cdk5-immunoreactive inclusions that colocalized with phosphorylated tau in 70-80% of those fibers. Immunoelectronmicroscopy revealed the association of cdk5 with tau-immunoreactive PHFs. In all biopsies that contained them, regenerating muscle fibers had diffuse, moderate to strong cdk5 immunoreactivity. At all neuromuscular junctions, there was strong cdk5 immunoreactivity postsynaptically. Our study suggests that cdk5: (1) plays a role in IBM pathogenesis, possibly mediating phosphorylation of PHF-related tau; (2) is involved in muscle regeneration; and (3) has a novel function at normal neuromuscular junctions. (C) 2000 Published by Elsevier Science Ireland Ltd.