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Alpha-Synuclein RT-QuIC in Idiopathic Normal Pressure Hydrocephalus
Alfonso Fasano1,2,3,4,5, Ivan Martinez-Valbuena6, Paula Azevedo1,2,7
1Edmond J. Safra Program in Parkinson's Disease, Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, UHN, Toronto, Ontario, Canada.
Annals of Neurology
|September 12, 2022
Summary
Seven of 50 idiopathic normal pressure hydrocephalus patients had underlying synucleinopathy. These patients showed more frequent L-dopa responsiveness and wider gait base, indicating potential links between alpha-synuclein and hydrocephalus subtypes.
Area of Science:
- Neurology
- Neuroscience
- Biochemistry
Background:
- Idiopathic normal pressure hydrocephalus (iNPH) is a neurological disorder.
- The underlying cause of iNPH is not fully understood.
- Synucleinopathies, involving misfolded alpha-synuclein, are implicated in other neurodegenerative diseases.
Purpose of the Study:
- To quantify the prevalence of underlying synucleinopathy in patients with iNPH.
- To investigate potential clinical differences between iNPH patients with and without synucleinopathy.
Main Methods:
- Real-time quaking-induced conversion (RT-QuIC) assay used to detect alpha-synuclein in cerebrospinal fluid (CSF).
- CSF samples from 50 iNPH patients analyzed.
- Clinical data, including L-dopa responsiveness and gait parameters, compared between RT-QuIC positive and negative groups.
Main Results:
- Seven out of 50 (14%) iNPH patients tested positive for alpha-synuclein misfolding via RT-QuIC.
- RT-QuIC positive patients demonstrated significantly more frequent L-dopa responsiveness.
- Gait analysis revealed a wider base in positive cases, with less improvement in step length and velocity post-intervention compared to negative cases.
Conclusions:
- A subset of iNPH patients exhibit underlying synucleinopathy.
- Alpha-synuclein positivity may correlate with specific clinical features, including L-dopa responsiveness and gait characteristics.
- RT-QuIC is a valuable tool for identifying synucleinopathy in iNPH, potentially aiding in patient stratification and understanding disease mechanisms.

