Glycogen synthase kinase-3beta is associated with Parkinson's disease.

We immunohistochemically examined the expression of glycogen synthase kinase-3beta (GSK-3beta) in the brains of Parkinson's disease (PD) patients. GSK-3beta was localized in punctate structures in the cytosol of subsets of neurons in the midbrain and upper pons. GSK-3beta was also localized in Lewy bodies (LBs) as was phosphorylated GSK-3beta (Ser9) (pGSK-3beta (Ser9)). Both GSK-3beta and pGSK-3beta (Ser9) were localized specifically in the halo of LBs. The core of LBs was negative for GSK-3beta, while pGSK-3beta (Ser9) was present in only a small number of LB cores. Cortical LBs were positive for pGSK-3beta (Ser9) but not for GSK-3beta. Neither GSK-3beta nor pGSK-3beta (Ser9) was present in glial cytoplasmic inclusions (GCIs) in the brains of multiple system atrophy (MSA) patients. Our results suggest that GSK-3beta plays a role in the pathogenesis of PD but not in that of MSA.