ArticleFluids and barriers of the CNS2022
In vivo assessment of Lewy body and beta-amyloid copathologies in idiopathic normal pressure hydrocephalus: prevalence and associations with clinical features and surgery outcome.
Article in Fluids and barriers of the CNS, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed, 18 citations in OpenAlex.
- α-Synuclein Pathology in Idiopathic Normal Pressure Hydrocephalus: Evidence for Concomitant Synucleinopathy and Clinical Implications.Diagnostics (Basel, Switzerland) · 2026Review
- Alzheimer's disease core biomarkers are associated with worse baseline and postoperative cognitive profiles in idiopathic normal pressure hydrocephalus: findings from the Bologna PRO-Hydro study.Fluids and barriers of the CNS · 2026Article
- CSF alpha-Synuclein Seed Amplification Assay results in routine clinically collected samples.Journal of Parkinson's disease · 2026Article
- Intracranial inflammation and meningeal fibrosis are associated with perivascular changes, altered CSF tracer dynamics, and cognitive decline in a rat model of communicating hydrocephalus.Fluids and barriers of the CNS · 2026Article
- Investigation of the Determinants of Disease Severity in Patients with Idiopathic Normal Pressure Hydrocephalus.Movement disorders clinical practice · 2025Article
- Biomechanical instability of the brain-CSF interface in hydrocephalus.Brain : a journal of neurology · 2024Review
- The Bayesian approach for real-world implementation of plasma p-tau217 in tertiary care memory clinics in Thailand.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Freezing of gait in idiopathic normal pressure hydrocephalus.Fluids and barriers of the CNS · 2024Article
- α-Synuclein seeding activity in duodenum biopsies from Parkinson's disease patients.PLoS pathogens · 2023Article
- INPH and parkinsonism: A positive shunt response with a negative tap test.Frontiers in neurology · 2023Article
- Refining the diagnostic evaluation of idiopathic normal pressure hydrocephalus with Alzheimer's and α-synuclein biomarkers.Frontiers in neurologyArticle
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Authors and funding
17 authors at 4 institutions in 2 countries.
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Abstract
backgroundIdiopathic normal pressure hydrocephalus (iNPH) is a clinico-radiological syndrome of elderly individuals likely sustained by different neurodegenerative changes as copathologies. Since iNPH is a potentially reversible condition, assessing neurodegenerative pathologies in vitam through CSF biomarkers and their influence on clinical features and surgical outcome represents crucial steps.
methodsWe measured α-synuclein seeding activity related to Lewy body (LB) pathology by the real-time quaking-induced conversion assay (RT-QuIC) and Alzheimer disease core biomarkers (proteins total-tau, phospho-tau, and amyloid-beta) by immunoassays in the cerebrospinal fluid (CSF) of 293 iNPH patients from two independent cohorts. To compare the prevalence of LB copathology between iNPH participants and a control group representative of the general population, we searched for α-synuclein seeding activity in 89 age-matched individuals who died of Creutzfeldt-Jakob disease (CJD). Finally, in one of the iNPH cohorts, we also measured the CSF levels of neurofilament light chain protein (NfL) and evaluated the association between all CSF biomarkers, baseline clinical features, and surgery outcome at 6 months.
resultsSixty (20.5%) iNPH patients showed α-synuclein seeding activity with no significant difference between cohorts. In contrast, the prevalence observed in CJD was only 6.7% (p = 0.002). Overall, 24.0% of iNPH participants showed an amyloid-positive (A+) status, indicating a brain co-pathology related to Aβ deposition. At baseline, in the Italian cohort, α-synuclein RT-QuIC positivity was associated with higher scores on axial and upper limb rigidity (p = 0.003 and p = 0.011, respectively) and lower MMSEc scores (p = 0.003). A+ patients showed lower scores on the MMSEc (p = 0.037) than A- patients. Higher NfL levels were also associated with lower scores on the MMSEc (rho = -0.213; p = 0.021). There were no significant associations between CSF biomarkers and surgical outcome at 6 months (i.e. responders defined by decrease of 1 point on the mRankin scale).
conclusionsPrevalent LB- and AD-related neurodegenerative pathologies affect a significant proportion of iNPH patients and contribute to cognitive decline (both) and motor impairment (only LB pathology) but do not significantly influence the surgical outcome at 6 months. Their effect on the clinical benefit after surgery over a more extended period remains to be determined.
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