Cerebrospinal fluid and plasma biomarkers in idiopathic normal pressure hydrocephalus: comparison with Alzheimer's and Parkinson's diseases.

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BackgroundIdiopathic normal pressure hydrocephalus (iNPH) is a potentially reversible neurological disorder whose diagnosis is complicated by clinical overlap with neurodegenerative diseases. Fluid biomarkers may provide insight into disease mechanisms and support differential diagnosis.MethodsWe performed a small exploratory study at the Neurology and Neurosurgery Sections of the University Hospital of Perugia, between 2024 and 2025, comparing cerebrospinal fluid (CSF) and plasma biomarkers among patients with iNPH, Alzheimer's disease (AD), Parkinson's disease (PD), and non-neurodegenerative controls (CTRL). CSF concentrations of amyloid-β peptides (Aβ42, Aβ40, Aβ42/Aβ40 ratio), tau proteins (p-tau 181 and t-tau) and neurofilament light chain (NfL) were measured. In plasma, amyloid-β peptides (Aβ42, Aβ40, Aβ42/Aβ40 ratio), tau proteins (p-tau 217), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) were assessed. Both CSF and plasma biomarkers were measured using standardized immunoassays. Group differences and correlations between CSF and plasma biomarkers were analyzed.ResultsCSF Aβ40 levels were significantly lower in iNPH compared with all other groups (all p p = 0.001) and PD (p = 0.009), while CSF p-tau181 and t-tau were decreased compared with AD (p p ≤ 0.024). The CSF Aβ42/Aβ40 ratio remained preserved in iNPH, distinguishing it from AD (p r = 0.77, p = 0.0012), whereas plasma amyloid biomarkers poorly reflected CSF concentrations.ConclusionsiNPH is associated with low CSF Aβ40 levels, possibly reflecting altered CSF dynamics rather than a primary pathophysiological mechanism. In iNPH, plasma NfL showed a preliminary correlation with CSF NfL; however, larger age-adjusted studies are required before peripheral markers can be considered clinically informative in this setting.

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