Cutaneous nerve fiber pathology and function in Parkinson’s disease and atypical parkinsonism: a cohort study

Mattias Andréasson; Wojciech Paslawski; Astrid Juhl Terkelsen; Kristin Samuelsson; Henrik Zetterberg; Kaj Blennow; Páll Karlsson; Per Svenningsson

doi:10.1038/s41531-025-01030-y

Cutaneous nerve fiber pathology and function in Parkinson’s disease and atypical parkinsonism: a cohort study

Mattias Andréasson^*
, Wojciech Paslawski
, Astrid Juhl Terkelsen
, Kristin Samuelsson
, Henrik Zetterberg
, Kaj Blennow
, Páll Karlsson
, Per Svenningsson

^*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

Abstract

There is scientific evidence for ongoing neurodegeneration and alpha-synuclein pathology involving the peripheral nervous system in Parkinson’s disease (PD) and multiple system atrophy (MSA). We explored putative disease-mirroring properties of cutaneous nerve fibers in patients with PD (n = 20), MSA (n = 12), four-repeat tauopathies (n = 11), and controls (n = 20). Assessments included clinical rating scales, blood sampling, sudomotor testing, skin punch biopsies from the neck and leg, and 1-year follow-up. Skin alpha-synuclein seeding amplification assay (SAA) and determination of intraepidermal nerve fiber density (IENFD) were performed. Reduced electrochemical skin conductance was evident in MSA, associated with clinical rating scores. Cervical skin SAA (PD vs controls) achieved a 100% sensitivity and 70% specificity for detecting PD. We found no difference in baseline IENFD, nor in 1-year changes, in patients relative to controls. Baseline IENFD, plasma neurofilament light, and SAA kinetics associated with 1-year clinical disease progression in MSA. Skin may harbor promising prognostic properties in MSA.

Original language	English
Article number	170
Journal	npj Parkinson's Disease
Volume	11
Issue	1
ISSN	2373-8057
DOIs	https://doi.org/10.1038/s41531-025-01030-y
Publication status	Published - Dec 2025

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title = "Cutaneous nerve fiber pathology and function in Parkinson{\textquoteright}s disease and atypical parkinsonism: a cohort study",

abstract = "There is scientific evidence for ongoing neurodegeneration and alpha-synuclein pathology involving the peripheral nervous system in Parkinson{\textquoteright}s disease (PD) and multiple system atrophy (MSA). We explored putative disease-mirroring properties of cutaneous nerve fibers in patients with PD (n = 20), MSA (n = 12), four-repeat tauopathies (n = 11), and controls (n = 20). Assessments included clinical rating scales, blood sampling, sudomotor testing, skin punch biopsies from the neck and leg, and 1-year follow-up. Skin alpha-synuclein seeding amplification assay (SAA) and determination of intraepidermal nerve fiber density (IENFD) were performed. Reduced electrochemical skin conductance was evident in MSA, associated with clinical rating scores. Cervical skin SAA (PD vs controls) achieved a 100\% sensitivity and 70\% specificity for detecting PD. We found no difference in baseline IENFD, nor in 1-year changes, in patients relative to controls. Baseline IENFD, plasma neurofilament light, and SAA kinetics associated with 1-year clinical disease progression in MSA. Skin may harbor promising prognostic properties in MSA.",

author = "Mattias Andr{\'e}asson and Wojciech Paslawski and Terkelsen, \{Astrid Juhl\} and Kristin Samuelsson and Henrik Zetterberg and Kaj Blennow and P{\'a}ll Karlsson and Per Svenningsson",

year = "2025",

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doi = "10.1038/s41531-025-01030-y",

language = "English",

volume = "11",

journal = "npj Parkinson's Disease ",

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Cutaneous nerve fiber pathology and function in Parkinson’s disease and atypical parkinsonism: a cohort study. / Andréasson, Mattias; Paslawski, Wojciech; Terkelsen, Astrid Juhl et al.
In: npj Parkinson's Disease , Vol. 11, No. 1, 170, 12.2025.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Cutaneous nerve fiber pathology and function in Parkinson’s disease and atypical parkinsonism

T2 - a cohort study

AU - Andréasson, Mattias

AU - Paslawski, Wojciech

AU - Terkelsen, Astrid Juhl

AU - Samuelsson, Kristin

AU - Zetterberg, Henrik

AU - Blennow, Kaj

AU - Karlsson, Páll

AU - Svenningsson, Per

PY - 2025/12

Y1 - 2025/12

N2 - There is scientific evidence for ongoing neurodegeneration and alpha-synuclein pathology involving the peripheral nervous system in Parkinson’s disease (PD) and multiple system atrophy (MSA). We explored putative disease-mirroring properties of cutaneous nerve fibers in patients with PD (n = 20), MSA (n = 12), four-repeat tauopathies (n = 11), and controls (n = 20). Assessments included clinical rating scales, blood sampling, sudomotor testing, skin punch biopsies from the neck and leg, and 1-year follow-up. Skin alpha-synuclein seeding amplification assay (SAA) and determination of intraepidermal nerve fiber density (IENFD) were performed. Reduced electrochemical skin conductance was evident in MSA, associated with clinical rating scores. Cervical skin SAA (PD vs controls) achieved a 100% sensitivity and 70% specificity for detecting PD. We found no difference in baseline IENFD, nor in 1-year changes, in patients relative to controls. Baseline IENFD, plasma neurofilament light, and SAA kinetics associated with 1-year clinical disease progression in MSA. Skin may harbor promising prognostic properties in MSA.

AB - There is scientific evidence for ongoing neurodegeneration and alpha-synuclein pathology involving the peripheral nervous system in Parkinson’s disease (PD) and multiple system atrophy (MSA). We explored putative disease-mirroring properties of cutaneous nerve fibers in patients with PD (n = 20), MSA (n = 12), four-repeat tauopathies (n = 11), and controls (n = 20). Assessments included clinical rating scales, blood sampling, sudomotor testing, skin punch biopsies from the neck and leg, and 1-year follow-up. Skin alpha-synuclein seeding amplification assay (SAA) and determination of intraepidermal nerve fiber density (IENFD) were performed. Reduced electrochemical skin conductance was evident in MSA, associated with clinical rating scores. Cervical skin SAA (PD vs controls) achieved a 100% sensitivity and 70% specificity for detecting PD. We found no difference in baseline IENFD, nor in 1-year changes, in patients relative to controls. Baseline IENFD, plasma neurofilament light, and SAA kinetics associated with 1-year clinical disease progression in MSA. Skin may harbor promising prognostic properties in MSA.

UR - https://www.scopus.com/pages/publications/105007999626

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DO - 10.1038/s41531-025-01030-y

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JO - npj Parkinson's Disease

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IS - 1

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ER -

Cutaneous nerve fiber pathology and function in Parkinson’s disease and atypical parkinsonism: a cohort study

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