PLA2G6 accumulates in Lewy bodies in PARK14 and idiopathic Parkinson's disease

The histopathological hallmark of Parkinson's disease (PD) and dementia with Lewy bodies (DLB) is the occurrence of insoluble fibrillary aggregates known as Lewy bodies, in which phosphorylated alpha-synuclein (alpha-syn) is a major component. To date, familial PD-linked gene products, including a-syn, parkin, PINK-1, DJ-1 and LRRK2, are known to be involved in Lewy body formation. Phospholipase A(2), group VI (PLA2G6) is the causative gene for PARKI4-linked parkinsonism (PARK14), a familial form of juvenile-onset dystonia parkinsonism. Several lines of evidence have suggested that PLA2G6 might play a role in the pathogenesis of not only PARK14, but also idiopathic PD. However, no published studies have investigated the association of PLA2G6 with the formation of Lewy bodies. In the present study, we used immunohistochemistiy and Western blotting to investigate the involvement of PLA2G6 in Lewy body disease (PD and DLB), multiple system atrophy and Alzheimer's disease, in comparison with normal controls. Although cortical Lewy bodies, which lack a definable central core, were unstained with anti-PLA2G6 antibodies, the cores of brainstem-type Lewy bodies from PARK14 and idiopathic PD patients were moderately or intensely immunopositive for PLA2G6. Our results further reinforce the association of PLA2G6 with the pathogenesis of idiopathic PD, in addition to PARK14. (C) 2017 Elsevier B.V. All rights reserved.