Absence of Lewy body pathology in the form of Parkinson disease (PD) caused by mutations in the LRRK2 gene does not equate to a lack of α-synuclein pathology, two new studies have shown. The findings, which were published in parallel in Acta Neuropathologica, resolve uncertainty about the involvement of α-synuclein in this form of PD and present new opportunities for research and therapy.

Mutations in LRRK2, which encodes leucine-rich repeat kinase 2, are the most common cause of genetic PD. Although the clinical presentation of LRRK2-related PD (LRRK2-PD) is largely the same as that of idiopathic PD, the pathology differs: LRRK2-PD often lacks the Lewy body pathology that is characteristic of idiopathic PD. This difference has raised questions about the involvement of α-synuclein, the aggregation of which leads to Lewy body formation.