Tags

Type your tag names separated by a space and hit enter

CSF biomarkers distinguish idiopathic normal pressure hydrocephalus from its mimics.
J Neurol Neurosurg Psychiatry. 2019 10; 90(10):1117-1123.JN

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.

Authors+Show Affiliations

Hydrocephalus Research Unit, Department of clinical neuroscience, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden anna.jeppsson@gu.se. Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.Hydrocephalus Research Unit, Department of clinical neuroscience, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden. Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK. UK Dementia Research Institute at UCL, London, UK.Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.Unit of Clinical Neuroscience, Neurology, University of Oulu, Oulu, Finland. Medical Research Center, Oulu University Hospital, Oulu, Finland.Department of Neurology, Kuopio University Hospital and University of Eastern Finland, Kuopio, Finland.Department of Pathology, Kuopio University Hospital and University of Eastern Finland, Kuopio, Finland.Department of Acute Internal Medicine and Geriatrics, Linköping University, Linköping, Sweden.Medical Research Center, Oulu University Hospital, Oulu, Finland. Unit of Clinical Neuroscience, Neurosurgery, University of Oulu, Oulu, Finland. Department of Neurosurgery, Kuopio University Hospital and University of Eastern Finland, Kuopio, Finland.Hydrocephalus Research Unit, Department of clinical neuroscience, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31167811

Citation

Jeppsson, Anna, et al. "CSF Biomarkers Distinguish Idiopathic Normal Pressure Hydrocephalus From Its Mimics." Journal of Neurology, Neurosurgery, and Psychiatry, vol. 90, no. 10, 2019, pp. 1117-1123.
Jeppsson A, Wikkelsö C, Blennow K, et al. CSF biomarkers distinguish idiopathic normal pressure hydrocephalus from its mimics. J Neurol Neurosurg Psychiatry. 2019;90(10):1117-1123.
Jeppsson, A., Wikkelsö, C., Blennow, K., Zetterberg, H., Constantinescu, R., Remes, A. M., Herukka, S. K., Rauramaa, T., Nagga, K., Leinonen, V., & Tullberg, M. (2019). CSF biomarkers distinguish idiopathic normal pressure hydrocephalus from its mimics. Journal of Neurology, Neurosurgery, and Psychiatry, 90(10), 1117-1123. https://doi.org/10.1136/jnnp-2019-320826
Jeppsson A, et al. CSF Biomarkers Distinguish Idiopathic Normal Pressure Hydrocephalus From Its Mimics. J Neurol Neurosurg Psychiatry. 2019;90(10):1117-1123. PubMed PMID: 31167811.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CSF biomarkers distinguish idiopathic normal pressure hydrocephalus from its mimics. AU - Jeppsson,Anna, AU - Wikkelsö,Carsten, AU - Blennow,Kaj, AU - Zetterberg,Henrik, AU - Constantinescu,Radu, AU - Remes,Anne M, AU - Herukka,Sanna-Kaisa, AU - Rauramaa,Tuomas, AU - Nagga,Katarina, AU - Leinonen,Ville, AU - Tullberg,Mats, Y1 - 2019/06/05/ PY - 2019/03/18/received PY - 2019/04/29/revised PY - 2019/05/12/accepted PY - 2019/6/7/pubmed PY - 2020/6/19/medline PY - 2019/6/7/entrez KW - Alzheimer’s disease KW - CSF KW - Multiple systems atrophy KW - Parkinson’s disease KW - Progressive supranuclear palsy KW - biomarkers KW - corticobasal degeneration KW - frontotemporal dementia KW - idiopathic normal pressure hydrocephalus KW - vascular dementia SP - 1117 EP - 1123 JF - Journal of neurology, neurosurgery, and psychiatry JO - J Neurol Neurosurg Psychiatry VL - 90 IS - 10 N2 - 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. SN - 1468-330X UR - https://www.unboundmedicine.com/medline/citation/31167811/CSF_biomarkers_distinguish_idiopathic_normal_pressure_hydrocephalus_from_its_mimics_ L2 - https://jnnp.bmj.com/lookup/pmidlookup?view=long&pmid=31167811 DB - PRIME DP - Unbound Medicine ER -