Negative α-synuclein pathology in the submandibular gland of patients carrying PRKN pathogenic variants

Abstract

Introduction: Alpha-synuclein (AS) pathology in the peripheral nervous tissue is a potential pathological biomarker in Parkinson disease (PD). Several studies reported the excellent specificity of the AS pathology of the submandibular gland (SMG) biopsy in PD. PRKN pathogenic variant is one of the major genetic causes of young-onset PD without Lewy pathology in the brain. In this study, we evaluated peripheral AS pathology in the SMG biopsy of patients with PRKN pathogenic variants.

Methods: We enrolled three young-onset PD patients with PRKN pathogenic variants. Two patients were compound heterozygous for trans-exon 3 and 4 deletions and one patient was heterozygous for an exon 2 duplication. We obtained two submandibular gland tissues with core needle biopsy (18G). The neural structures were identified using neurofilament (NF) immunostaining and the neural tissue in the adjacent section were stained with 129 phophorylated α-synuclein (pAS) antibody.

Results: pAS staining in the SMG was negative in all cases with the PRKN pathogenic variants.

Conclusions: Our data may support the high specificity of the AS pathology of SMG in α-synuclein associated parkinsonism. Future studies evaluating peripheral neural tissue including the SMG in the elderly healthy population are required to validate the role of peripheral AS pathology as a biomarker in PD.

Keywords: Lewy body pathology; PRKN pathogenic Variant; Submandibular gland biopsy; α-synuclein.