Figure 3.

Abnormal α-syn aggregates characterized by a combination of different primary antibodies. Confocal microscope study (x400) of α-syn aggregates in patients with different variants of synucleinopathy based on a co-localization between p-syn and a neuronal marker (i.e. PGP) or antibodies against abnormal α-syn epitopes expression of C-terminal post-translational modifications or amyloid fibrils (syn-F1). (A) P-syn demonstrated an excellent co-localization with PGP (A^I) in a nerve plexus supporting the intraneural deposition of abnormal α-syn aggregates (A^II). (B) The co-localization in a nerve plexus between p-syn and syn-F1 (B^I) found in the majority of analysed deposits supporting the fibrillar nature of these aggregates (B^II). (C) Sudomotor fibers around a sweat tubule marked by NAC (C^I) were co-localized with p-syn (arrow in C^II) although other sudomotor fibers stained by p-syn were devoid of NAC staining (asterisk in C^II). (D) NY-syn staining was occasionally seen in non-synaptic fibers (D^I) and this staining co-localized with p-syn (D^II). The four different coexistent fibrillar and non-fibrillar α-syn deposits found in skin nerves were similarly distributed among different clinical phenotypes. Nevertheless, these deposits showed important differences in specific variants of synucleinopathy such as their localisation (i.e. only in somatosensory skin fibers in MSA - see Table 2) or the widespread involvement of autonomic annexes (i.e. in PAF and DLB - see Fig. 4). These differences may support a different pathogenesis among synucleinopathies helping to identify specific diagnostic traits.