Phosphorylated alpha-synuclein in Iba1-positive macrophages in the skin of patients with Parkinson's disease

Background: Increasing evidence suggests that alpha-synuclein (alpha Syn) accumulation in cholinergic and adrenergic fibers in the skin is a useful biomarker to diagnose idiopathic Parkinson's disease (IPD). It has been widely reported that phosphorylated alpha Syn (p-alpha Syn) deposits in autonomic fibers in IPD are a biomarker in the skin, but other tissue localizations have not been fully investigated. Objective: It has been previously suggested that alpha Syn aggregates activate peripheral macrophages and that peripheral macrophages ingest pathological alpha syn aggregates in aged rats or IPD patients. However, it remains to be elucidated whether peripheral macrophages in the skin of IPD patients accumulate alpha Syn. We evaluated whether (1) p-alpha Syn deposits in dermal macrophages might represent a useful biomarker for IPD and (2) dermal macrophages play a role in the underlying pathogenesis of IPD. Methods: We performed an immunohistological analysis of skin biopsy specimens from IPD patients and controls. Results: We found that (1) p-alpha Syn accumulation is present in dermal macrophages in skin biopsy specimens from patients with IPD, (2) not only dermal adrenergic fibers with p-alpha Syn deposits but also dermal macrophages with p-alpha Syn deposits are useful biomarkers for IPD patients and (3) the number of macrophages was significantly positively correlated with the number of macrophages with p-alpha Syn deposits in the dermis of IPD patients. Interpretation: Our results suggest that dermal macrophages, which are innate immune cells, play an important role in IPD patients and are a novel biomarker for IPD.

Automated summary

The study suggests that p-alpha Syn accumulation in dermal macrophages is present in patients with IPD and may serve as an important biomarker for the disease. Additionally, the number of dermal macrophages was significantly positively correlated with the number of macrophages with p-alpha Syn deposits in the dermis of IPD patients.