NeuralCipher Research overview
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BackgroundThe pathophysiology of idiopathic normal pressure hydrocephalus (iNPH) and its association with neurodegenerative disorders is poorly understood.ObjectivesThe aim was to determine the prevalence of α-synuclein pathology in iNPH and its associations with clinical characteristics.MethodsWe 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.ResultsA 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.ConclusionsUnderlying 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.
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