University of Oulu

Lukkarinen, H., Jeppsson, A., Wikkelsö, C. et al. Cerebrospinal fluid biomarkers that reflect clinical symptoms in idiopathic normal pressure hydrocephalus patients. Fluids Barriers CNS 19, 11 (2022). https://doi.org/10.1186/s12987-022-00309-z

Cerebrospinal fluid biomarkers that reflect clinical symptoms in idiopathic normal pressure hydrocephalus patients

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Author: Lukkarinen, Heikki1; Jeppsson, Anna2,3; Wikkelsö, Carsten2,3;
Organizations: 1Department of Neurosurgery, Institute of Clinical Medicine – Neurosurgery, Kuopio University Hospital and University of Eastern Finland, Kuopio, Finland
2Hydrocephalus Research Unit, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
3Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
4Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
5Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden
6Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK
7UK Dementia Research Institute at UCL, London, UK
8Hong Kong Center for Neurodegenerative Diseases, Hong Kong, China
9Unit of Clinical Neuroscience, Neurology, University of Oulu, Oulu, Finland
10Medical Research Center, Oulu University Hospital, Oulu, Finland
11Department of Neurology, Kuopio University Hospital and University of Eastern Finland, Kuopio, Finland
12Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland
13Department of Pathology, Kuopio University Hospital and University of Eastern Finland, Kuopio, Finland
14Department of Acute Internal Medicine and Geriatrics, Linköping University, Linköping, Sweden
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.5 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2022060342766
Language: English
Published: Springer Nature, 2022
Publish Date: 2022-08-04
Description:

Abstract

Background:The relationship between cerebrospinal fluid (CSF) biomarkers and the clinical features of idiopathic normal pressure hydrocephalus (iNPH) has been inconclusive. We aimed to evaluate CSF biomarkers reflecting Alzheimer’s disease (AD)-related amyloid β (Aβ) aggregation, tau pathology, neuroinflammation and axonal degeneration in relation to the clinical features of pre- and post-shunt surgery in iNPH patients.

Methods:Mini Mental State Examination (MMSE) scores and gait velocity were evaluated pre- and postoperatively in cohorts of 65 Finnish (FIN) and 82 Swedish (SWE) iNPH patients. Lumbar CSF samples were obtained prior to shunt surgery and analysed for soluble amyloid precursor protein alpha (sAPPα) and beta (sAPPβ); amyloid-β isoforms of 42, 40 and 38 (Aβ42, Aβ40, Aβ38); total tau (T-tau); phosphorylated tau (P-tau181); neurofilament light (NfL) and monocyte chemoattractant protein 1 (MCP1).

Results:Preoperative patient characteristics showed no significant differences between patients in the FIN and SWE cohorts. Patients in both cohorts had significantly improved gait velocity after shunt surgery (p < 0.0001). Low CSF T-tau and absence of apolipoprotein E ε4 predicted over 20% gait improvement postoperatively (p = 0.043 and p = 0.008). Preoperative CSF T-tau, P-tau181 and NfL correlated negatively with MMSE scores both pre- (p < 0.01) and post-surgery (p < 0.01). Furthermore, T-tau, NfL and Aβ₄₂ correlated with MMSE outcomes (p < 0.05). Low preoperative CSF P-tau181 (p = 0.001) and T-tau with NfL (p < 0.001 and p = 0.049) best predicted pre- and postoperative MMSE scores greater than or equal to 26.

Conclusions:CSF biomarkers of neurodegeneration appeared to correlate with pre- and postoperative cognition, providing a window into neuropathological processes. In addition, preoperative CSF neurodegeneration biomarkers may have potential in the prediction of gait and cognitive outcomes after shunt surgery.

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Series: Fluids and barriers of the CNS
ISSN: 2045-8118
ISSN-E: 2045-8118
ISSN-L: 2045-8118
Volume: 19
Article number: 11
DOI: 10.1186/s12987-022-00309-z
OADOI: https://oadoi.org/10.1186/s12987-022-00309-z
Type of Publication: A1 Journal article – refereed
Field of Science: 3124 Neurology and psychiatry
Subjects:
Funding: The study was funded by Kuopio University Hospital VTR (#5252614) fund, Academy of Finland (#339767) and Sigrid Juselius Foundation.
Copyright information: © The Author(s) 2022. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/ publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
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