Weber Sandrina, Farris Carly M, Ma Yihua, Dakna Mohammed, Starke Maritta, Schade Sebastian, Bartl Michael, Trenkwalder Claudia, Concha-Marambio Luis, Mollenhauer Brit
Department of Neurology, University Medical Center Goettingen, Goettingen, Germany.
Paracelsus-Elena-Klinik, Kassel, Germany.
Mov Disord. 2025 Jun;40(6):1206-1213. doi: 10.1002/mds.30184. Epub 2025 Apr 9.
The pathophysiology of idiopathic normal pressure hydrocephalus (iNPH) and its association with neurodegenerative disorders is poorly understood.
The aim was to determine the prevalence of α-synuclein pathology in iNPH and its associations with clinical characteristics.
We used α-synuclein seed amplification assay (synSAA) to retrospectively analyze cerebrospinal fluid (CSF) from a large single-center iNPH cohort (n = 144). Clinical assessments comprised Unified Parkinson's Disease Rating Scale part III, Mini-Mental State Examination, levodopa-challenge test, and olfactory identification test. Degenerative biomarkers (total-tau, phospho-tau, β-amyloid 1-42, and β-amyloid 1-40) were measured in CSF.
A total of 30.1% of iNPH patients were synSAA+, and presented significantly more upper limb (UL) rigidity, hallucinations, and worse olfactory performance than synSAA- cases. Anosmia was higher in synSAA+ patients (64.0%) than synSAA- patients (15.3%). Clinical assessments and other biomarkers did not significantly vary with synSAA status.
Underlying α-synuclein pathology is common in iNPH and presents with UL rigidity and olfactory dysfunction, suggesting a distinct synSAA+ phenotype in iNPH. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
特发性正常压力脑积水（iNPH）的病理生理学及其与神经退行性疾病的关联尚不清楚。
旨在确定iNPH中α-突触核蛋白病理的患病率及其与临床特征的关联。
我们使用α-突触核蛋白种子扩增检测（synSAA）对来自一个大型单中心iNPH队列（n = 144）的脑脊液（CSF）进行回顾性分析。临床评估包括统一帕金森病评定量表第三部分、简易精神状态检查、左旋多巴激发试验和嗅觉识别测试。在脑脊液中测量退行性生物标志物（总tau蛋白、磷酸化tau蛋白、β-淀粉样蛋白1-42和β-淀粉样蛋白1-40）。
共有30.1%的iNPH患者为synSAA阳性，与synSAA阴性患者相比，上肢（UL）僵硬、幻觉症状更明显，嗅觉表现更差。synSAA阳性患者的嗅觉丧失率（64.0%）高于synSAA阴性患者（15.3%）。临床评估和其他生物标志物随synSAA状态无显著差异。
iNPH中潜在的α-突触核蛋白病理很常见，表现为上肢僵硬和嗅觉功能障碍，提示iNPH中存在一种独特的synSAA阳性表型。© 2025作者。由Wiley Periodicals LLC代表国际帕金森和运动障碍协会出版的《运动障碍》。
