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

<div><p>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 pa...

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محفوظ في:
التفاصيل البيبلوغرافية
المؤلف الرئيسي: V. Donadio (18628783) (author)
مؤلفون آخرون: A. Incensi (18628786) (author), O. El-Agnaf (18628789) (author), G. Rizzo (18628792) (author), N. Vaikath (18628795) (author), F. Del Sorbo (18628798) (author), C. Scaglione (18628801) (author), S. Capellari (12074707) (author), A. Elia (7413308) (author), M. Stanzani Maserati (18628804) (author), R. Pantieri (18628807) (author), R. Liguori (8202969) (author)
منشور في: 2018
الموضوعات:
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author V. Donadio (18628783)
author2 A. Incensi (18628786)
O. El-Agnaf (18628789)
G. Rizzo (18628792)
N. Vaikath (18628795)
F. Del Sorbo (18628798)
C. Scaglione (18628801)
S. Capellari (12074707)
A. Elia (7413308)
M. Stanzani Maserati (18628804)
R. Pantieri (18628807)
R. Liguori (8202969)
author2_role author
author
author
author
author
author
author
author
author
author
author
author_facet V. Donadio (18628783)
A. Incensi (18628786)
O. El-Agnaf (18628789)
G. Rizzo (18628792)
N. Vaikath (18628795)
F. Del Sorbo (18628798)
C. Scaglione (18628801)
S. Capellari (12074707)
A. Elia (7413308)
M. Stanzani Maserati (18628804)
R. Pantieri (18628807)
R. Liguori (8202969)
author_role author
dc.creator.none.fl_str_mv V. Donadio (18628783)
A. Incensi (18628786)
O. El-Agnaf (18628789)
G. Rizzo (18628792)
N. Vaikath (18628795)
F. Del Sorbo (18628798)
C. Scaglione (18628801)
S. Capellari (12074707)
A. Elia (7413308)
M. Stanzani Maserati (18628804)
R. Pantieri (18628807)
R. Liguori (8202969)
dc.date.none.fl_str_mv 2018-09-24T03:00:00Z
dc.identifier.none.fl_str_mv 10.1038/s41598-018-32588-8
dc.relation.none.fl_str_mv https://figshare.com/articles/journal_contribution/Skin_-synuclein_deposits_differ_in_clinical_variants_of_synucleinopathy_an_in_vivo_study/25919467
dc.rights.none.fl_str_mv CC BY 4.0
info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv Biomedical and clinical sciences
Neurosciences
Synucleinopathies
Skin Nerves
Pure Autonomic Failure (PAF)
Dementia With Lewy Bodies (DLB)
Autonomic Fibers
dc.title.none.fl_str_mv Skin α-synuclein deposits differ in clinical variants of synucleinopathy: an in vivo study
dc.type.none.fl_str_mv Text
Journal contribution
info:eu-repo/semantics/publishedVersion
text
contribution to journal
description <div><p>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.</p><p> </p></div><h2>Other Information</h2> <p> Published in: Scientific Reports<br> License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1038/s41598-018-32588-8" target="_blank">https://dx.doi.org/10.1038/s41598-018-32588-8</a></p>
eu_rights_str_mv openAccess
id Manara2_313a659a4f7d3c47573e29e47d14a2be
identifier_str_mv 10.1038/s41598-018-32588-8
network_acronym_str Manara2
network_name_str Manara2
oai_identifier_str oai:figshare.com:article/25919467
publishDate 2018
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rights_invalid_str_mv CC BY 4.0
spelling Skin α-synuclein deposits differ in clinical variants of synucleinopathy: an in vivo studyV. Donadio (18628783)A. Incensi (18628786)O. El-Agnaf (18628789)G. Rizzo (18628792)N. Vaikath (18628795)F. Del Sorbo (18628798)C. Scaglione (18628801)S. Capellari (12074707)A. Elia (7413308)M. Stanzani Maserati (18628804)R. Pantieri (18628807)R. Liguori (8202969)Biomedical and clinical sciencesNeurosciencesSynucleinopathiesSkin NervesPure Autonomic Failure (PAF)Dementia With Lewy Bodies (DLB)Autonomic Fibers<div><p>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.</p><p> </p></div><h2>Other Information</h2> <p> Published in: Scientific Reports<br> License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1038/s41598-018-32588-8" target="_blank">https://dx.doi.org/10.1038/s41598-018-32588-8</a></p>2018-09-24T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1038/s41598-018-32588-8https://figshare.com/articles/journal_contribution/Skin_-synuclein_deposits_differ_in_clinical_variants_of_synucleinopathy_an_in_vivo_study/25919467CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/259194672018-09-24T03:00:00Z
spellingShingle Skin α-synuclein deposits differ in clinical variants of synucleinopathy: an in vivo study
V. Donadio (18628783)
Biomedical and clinical sciences
Neurosciences
Synucleinopathies
Skin Nerves
Pure Autonomic Failure (PAF)
Dementia With Lewy Bodies (DLB)
Autonomic Fibers
status_str publishedVersion
title Skin α-synuclein deposits differ in clinical variants of synucleinopathy: an in vivo study
title_full Skin α-synuclein deposits differ in clinical variants of synucleinopathy: an in vivo study
title_fullStr Skin α-synuclein deposits differ in clinical variants of synucleinopathy: an in vivo study
title_full_unstemmed Skin α-synuclein deposits differ in clinical variants of synucleinopathy: an in vivo study
title_short Skin α-synuclein deposits differ in clinical variants of synucleinopathy: an in vivo study
title_sort Skin α-synuclein deposits differ in clinical variants of synucleinopathy: an in vivo study
topic Biomedical and clinical sciences
Neurosciences
Synucleinopathies
Skin Nerves
Pure Autonomic Failure (PAF)
Dementia With Lewy Bodies (DLB)
Autonomic Fibers