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CSF biomarkers distinguish idiopathic normal pressure hydrocephalus from its mimics

Journal article
Authors Anna Jeppsson
Carsten Wikkelsö
Kaj Blennow
Henrik Zetterberg
Radu Constantinescu
A. M. Remes
S. K. Herukka
T. Rauramaa
K. Nagga
V. Leinonen
Mats Tullberg
Published in Journal of Neurology, Neurosurgery and Psychiatry
ISSN 0022-3050
Publication year 2019
Published at Institute of Neuroscience and Physiology, Department of Physiology
Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Institute of Neuroscience and Physiology, Department of Clinical Neuroscience
Language en
Links dx.doi.org/10.1136/jnnp-2019-320826
Keywords Alzheimer's disease, biomarkers, corticobasal degeneration, CSF, frontotemporal dementia, idiopathic normal pressure hydrocephalus, Multiple systems atrophy, Parkinson's disease, Progressive supranuclear palsy, vascular dementia
Subject categories Neurosciences

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. © 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.

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Denna text är utskriven från följande webbsida:
http://www.gu.se/english/research/publication/?publicationId=282665
Utskriftsdatum: 2019-10-13