Skin α-synuclein deposits differ in clinical variants of synucleinopathy: an in vivo study

• Published in: Scientific reports Vol. 8; no. 1; pp. 14246 - 10
• Main Authors: Donadio, V., Incensi, A., El-Agnaf, O., Rizzo, G., Vaikath, N., Del Sorbo, F., Scaglione, C., Capellari, S., Elia, A., Stanzani Maserati, M., Pantieri, R., Liguori, R.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 24.09.2018; Nature Publishing Group
• Subjects: 13/1; 59/5; 692/53/2421; 692/617/375/365/1718; 96/106; 96/35; Aged; Aged, 80 and over; Aggregates; alpha-Synuclein - genetics; Amyloid; Amyloid - genetics; Amyloid - metabolism; Antibodies; Atrophy; Biopsy; Brain - metabolism; Brain - pathology; Conformation; Dementia; Dementia disorders; Deposits; Epitopes; Female; Fibers; Fibrils; Humanities and Social Sciences; Humans; Laboratories; Lewy bodies; Lewy Body Disease - genetics; Lewy Body Disease - metabolism; Lewy Body Disease - pathology; Localization; Male; multidisciplinary; Multiple System Atrophy - genetics; Multiple System Atrophy - metabolism; Multiple System Atrophy - pathology; Nerve Fibers - metabolism; Nerve Fibers - pathology; Nerves; Orthostatic hypotension; Parkinson Disease - genetics; Parkinson Disease - metabolism; Parkinson Disease - pathology; Parkinson's disease; Phosphorylation; Protein Aggregation, Pathological - genetics; Pure Autonomic Failure - genetics; Pure Autonomic Failure - metabolism; Pure Autonomic Failure - pathology; Science; Science (multidisciplinary); Serine; Skin; Skin - innervation; Skin - metabolism; Skin - pathology; Skin Diseases - diagnosis; Skin Diseases - genetics; Skin Diseases - metabolism; Skin Diseases - pathology; Synuclein; Dementia With Lewy Bodies (DLB); Synucleinopathies; Pure Autonomic Failure (PAF); Autonomic Fibers; Skin Nerves
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-32588-8

We aimed to characterize in vivo α-synuclein (α-syn) aggregates in skin nerves to ascertain: 1) the optimal marker to identify them; 2) possible differences between synucleinopathies that may justify the clinical variability. We studied multiple skin nerve α-syn deposits in 44 patients with synucleinopathy: 15 idiopathic Parkinson’s disease (IPD), 12 dementia with Lewy Bodies (DLB), 5 pure autonomic failure (PAF) and 12 multiple system atrophy (MSA). Ten healthy subjects were used as controls. Antibodies against native α-syn, C-terminal α-syn epitopes such as phosphorylation at serine 129 (p-syn) and to conformation-specific for α-syn mature amyloid fibrils (syn-F1) were used. We found that p-syn showed the highest sensitivity and specificity in disclosing skin α-syn deposits. In MSA abnormal deposits were only found in somatic fibers mainly at distal sites differently from PAF, IPD and DLB displaying α-syn deposits in autonomic fibers mainly at proximal sites. PAF and DLB showed the highest p-syn load with a widespread involvement of autonomic skin nerve fibers. In conclusion: 1) p-syn in skin nerves was the optimal marker for the in vivo diagnosis of synucleinopathies; 2) the localization and load differences of aggregates may help to identify specific diagnostic traits and support a different pathogenesis among synucleinopathies.