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CSF biomarkers distinguish idiopathic normal pressure hydrocephalus from its mimics

Jeppsson, A; Wikkelsö, C; Blennow, K; Zetterberg, H; Constantinescu, R; Remes, AM; Herukka, S-K; ... Tullberg, M; + view all (2019) CSF biomarkers distinguish idiopathic normal pressure hydrocephalus from its mimics. Journal of Neurology, Neurosurgery & Psychiatry , 90 (10) pp. 1117-1123. 10.1136/jnnp-2019-320826. Green open access

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Abstract

OBJECTIVE: To examine the differential diagnostic significance of cerebrospinal fluid (CSF) biomarkers reflecting Alzheimer's disease-related amyloid β (Aβ) production and aggregation, cortical neuronal damage, tau pathology, damage to long myelinated axons and astrocyte activation, which hypothetically separates patients with idiopathic normal pressure hydrocephalus (iNPH) from patients with other neurodegenerative disorders. METHODS: The study included lumbar CSF samples from 82 patients with iNPH, 75 with vascular dementia, 70 with Parkinson's disease, 34 with multiple system atrophy, 34 with progressive supranuclear palsy, 15 with corticobasal degeneration, 50 with Alzheimer's disease, 19 with frontotemporal lobar degeneration and 54 healthy individuals (HIs). We analysed soluble amyloid precursor protein alpha (sAPPα) and beta (sAPPβ), Aβ species (Aβ38, Aβ40 and Aβ42), total tau (T-tau), phosphorylated tau, neurofilament light and monocyte chemoattractant protein 1 (MCP-1). RESULTS: Patients with iNPH had lower concentrations of tau and APP-derived proteins in combination with elevated MCP-1 compared with HI and the non-iNPH disorders. T-tau, Aβ40 and MCP-1 together yielded an area under the curve of 0.86, differentiating iNPH from the other disorders. A prediction algorithm consisting of T-tau, Aβ40 and MCP-1 was designed as a diagnostic tool using CSF biomarkers. CONCLUSIONS: The combination of the CSF biomarkers T-tau, Aβ40 and MCP-1 separates iNPH from cognitive and movement disorders with good diagnostic sensitivity and specificity. This may have important implications for diagnosis and clinical research on disease mechanisms for iNPH.

Type: Article
Title: CSF biomarkers distinguish idiopathic normal pressure hydrocephalus from its mimics
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1136/jnnp-2019-320826
Publisher version: https://doi.org/10.1136/jnnp-2019-320826
Language: English
Additional information: © Author(s) (or their employer[s]) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license (http://creativecommons.org/licenses/by-nc/4.0/).
Keywords: Alzheimer’s disease, CSF, Multiple systems atrophy, Parkinson’s disease, Progressive supranuclear palsy, biomarkers, corticobasal degeneration, frontotemporal dementia, idiopathic normal pressure hydrocephalus, vascular dementia
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/10076879
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