Andréasson Mattias, Paslawski Wojciech, Terkelsen Astrid Juhl, Samuelsson Kristin, Zetterberg Henrik, Blennow Kaj, Karlsson Páll, Svenningsson Per
Center for Neurology, Academic Specialist Center, Stockholm, Sweden.
Department of Neurology, Karolinska University Hospital, Stockholm, Sweden.
NPJ Parkinsons Dis. 2025 Jun 15;11(1):170. doi: 10.1038/s41531-025-01030-y.
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.
有科学证据表明，帕金森病（PD）和多系统萎缩（MSA）中存在涉及外周神经系统的持续神经退行性变和α-突触核蛋白病理改变。我们探究了PD患者（n = 20）、MSA患者（n = 12）、四重复tau蛋白病患者（n = 11）和对照组（n = 20）皮肤神经纤维的假定疾病镜像特性。评估包括临床评分量表、血液采样、汗腺功能测试、颈部和腿部皮肤打孔活检以及1年随访。进行了皮肤α-突触核蛋白种子扩增试验（SAA）和表皮内神经纤维密度（IENFD）测定。MSA患者的电化学皮肤传导降低明显，与临床评分相关。颈部皮肤SAA（PD与对照组相比）在检测PD时灵敏度达到100%，特异性达到70%。我们发现患者与对照组相比，基线IENFD以及1年变化均无差异。基线IENFD、血浆神经丝轻链以及SAA动力学与MSA患者1年临床疾病进展相关。皮肤可能对MSA具有有前景的预后特性。
