Expression and distribution of alpha-synuclein pathology in the peripheral nerve fibers: a post-mortem study in Parkinson's disease patients

Parkinson’s disease (PD) is the second most common neurodegenerative disorder. It is characterized by degeneration of neurons and aggregation of the protein alpha-synuclein. Anatomically, this degenerative process affects many regions of the central nervous system, as well as the peripheral autonomic and enteric nervous systems. Increasing evidence suggests that the presence of aggregates of this protein in the peripheral nerve fibres can contribute to the development of early non motor symptoms. This study investigates the distribution and expression of pathological alpha- synuclein complexes in peripheral nerve fibres in post-mortem samples of the heart, adrenal gland and kidneys and gastro-intestinal tract. The analysed tissues derive from five body donors of the Body Donation Program of the Institute of Human Anatomy of the University of Padova, and include three patients with neuropathologically-confirmed Parkinson’s disease, and two neurologically-healthy controls. Immunofluorescence and immunoperoxidase staining was performed with conformation-specific antibodies for both the phosphorylated form of the alpha synuclein as well as oligomeric alpha-synuclein (clone 5G4), which mark the disease specific forms of the protein. Colocalization analysis with nerve markers neurofilament heavy chain polypeptide (NFH) and protein gene product 9.5 (PGP 9.5) was also performed. The adrenal gland and the heart displayed significant alpha-synuclein burden along nerve fibers, while the kidney presented a variable but distinct pattern. As expected, the tissues of the healthy controls resulted negative to both the antibodies. These findings confirm the presence of pathological alpha-synuclein aggregates in peripheral organs of PD patients and their role in the systemic aspects of the disease. Furthermore, the observed differential distribution among organs may reflect tissue-specific vulnerability or patterns of disease progression.