CSF biomarkers distinguish idiopathic normal pressure hydrocephalus from its mimics
|Author:||Jeppsson, Anna1,2; Wikkelsö, Carsten1,2; Blennow, Kaj3,4;|
1Hydrocephalus Research Unit, Department of clinical neuroscience, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
2Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
3Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
4Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden
5Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK
6UK Dementia Research Institute at UCL, London, UK
7Unit of Clinical Neuroscience, Neurology, University of Oulu, Oulu, Finland
8Medical Research Center, Oulu University Hospital, Oulu, Finland
9Department of Neurology, Kuopio University Hospital and University of Eastern Finland, Kuopio, Finland
10Department of Pathology, Kuopio University Hospital and University of Eastern Finland, Kuopio, Finland
11Department of Acute Internal Medicine and Geriatrics, Linköping University, Linköping, Sweden
12Unit of Clinical Neuroscience, Neurosurgery, University of Oulu, Oulu, Finland
13Department of Neurosurgery, Kuopio University Hospital and University of Eastern Finland, Kuopio, Finland
|Online Access:||PDF Full Text (PDF, 1.2 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe202003128100
|Publish Date:|| 2020-03-12
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.
Journal of neurology, neurosurgery and psychiatry
|Pages:||1117 - 1123|
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
3124 Neurology and psychiatry
This study was supported by grants from the Swedish Research Council (#2017-00915), Swedish State under the agreement between the Swedish government and the country councils, the ALF agreement (2017-04961; ALFGBG-720931, -720121 and ALFGBG715986), the Swedish Alzheimer Foundation (#AF-742881), Hjärnfonden, Sweden (#FO2017-0243), Kuopio University Hospital VTR-fund and the Göteborg Foundation for Neurological Research. HZ is a Wallenberg Academy Fellow. KB holds the Torsten Söderberg Professorship in Medicine at the Royal Swedish Academy of Sciences.
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