Phosphorylated α-synuclein and phosphorylated tau-protein in sural nerves may contribute to differentiate Parkinson's disease from multiple system atrophy and progressive supranuclear paralysis

Differential diagnosis of Parkinson's disease (PD), multiple system atrophy (MSA) and progressive supranuclear paralysis (PSP) is challenging. This study aimed to investigate the expression of phosphorylated alpha-synuclein (p-alpha-syn) and phosphorylated tau-protein (p-tau) in sural nerves from patients with PD, MSA and PSP to find biomarkers for differential diagnosis. Clinical evaluations and sural nerve biopsies were performed on 8 PD patients, 8 MSA patients, 6 PSP patients and 8 controls (CTRs). Toluidine blue staining was used to observe morphological changes in sural nerves. The deposition of p-alpha-syn and p-tau was detected by immunohistochemistry with semiquantitative evaluation. Locations of p-alpha-syn and p-tau were identified by double immunofluorescent staining. In case groups, the density of nerve fibres decreased with swollen or fragmented Schwann cells (SCs). All cases (22/22) but no CTRs (0/8) presented p-alpha-syn immunoreactivity with gradually decreasing semiquantitative levels among the PD (6.00 +/- 2.07), MSA (5.00 +/- 2.33) and PSP (3.50 +/- 1.52) groups. p-tau aggregates were found in 7/8 MSA (1.88 +/- 1.46) and 6/6 PSP (1.67 +/- 0.52) patients but not in PD patients or CTRs. There were different expression patterns of p-alpha-syn and p-tau in PD, MSA and PSP patients. These findings suggest that peripheral sensory nerve injury exists in PD, MSA and PSP patients. With a different expression pattern and level, p-alpha-syn and p-tau in sural nerves may serve as novel biomarkers for differential diagnosis of PD, MSA and PSP.