Novel cerebrospinal fluid biomarkers correlating with shunt responsiveness in patients with idiopathic normal pressure hydrocephalus.


Journal

Fluids and barriers of the CNS
ISSN: 2045-8118
Titre abrégé: Fluids Barriers CNS
Pays: England
ID NLM: 101553157

Informations de publication

Date de publication:
05 Jun 2023
Historique:
received: 07 03 2023
accepted: 09 05 2023
medline: 7 6 2023
pubmed: 6 6 2023
entrez: 5 6 2023
Statut: epublish

Résumé

Idiopathic Normal pressure hydrocephalus (iNPH) is a form of adult hydrocephalus that is clinically characterized by progressive gait impairment, cognitive dysfunction, and urinary incontinence. The current standard method of treatment involves surgical installation of a CSF diversion shunt. However, only a fraction of patients shows an alleviation of symptoms from shunt surgery. Thus, the purpose of this prospective explorative proteomic study was to identify prognostic CSF biomarkers to predict shunt responsiveness in iNPH patients. Further, we evaluated the ability of the core Alzheimer's disease (AD) CSF biomarkers phosphorylated (p)-tau, total (t)-tau, and amyloid-β 1-42 (Aβ We conducted a tandem mass tag (TMT) proteomic analysis of lumbar CSF from 68 iNPH patients, sampled pre-shunt surgery. Tryptic digests of CSF samples were labelled with TMTpro reagents. The TMT multiplex samples were fractionated in 24 concatenated fractions by reversed-phase chromatography at basic pH and analysed by liquid chromatography coupled to mass spectrometry (LC-MS) on an Orbitrap Lumos mass spectrometer. The relative abundances of the identified proteins were correlated with (i) iNPH grading scale (iNPHGS) and (ii) gait speed change 1 year after surgery from baseline to identify predictors of shunt responsiveness. We identified four CSF biomarker candidates which correlated most strongly with clinical improvement on the iNPHGS and were significantly changed in shunt-responsive compared to shunt-unresponsive iNPH patients 1 year post-surgery: FABP3 (R = - 0.46, log FABP3, MIF, ANXA4, B3GAT2, ITGB1, YWHAG, OLFM2, TGFBI and DSG2 in CSF are promising prognostic biomarker candidates to predict shunt responsiveness in iNPH patients.

Sections du résumé

BACKGROUND BACKGROUND
Idiopathic Normal pressure hydrocephalus (iNPH) is a form of adult hydrocephalus that is clinically characterized by progressive gait impairment, cognitive dysfunction, and urinary incontinence. The current standard method of treatment involves surgical installation of a CSF diversion shunt. However, only a fraction of patients shows an alleviation of symptoms from shunt surgery. Thus, the purpose of this prospective explorative proteomic study was to identify prognostic CSF biomarkers to predict shunt responsiveness in iNPH patients. Further, we evaluated the ability of the core Alzheimer's disease (AD) CSF biomarkers phosphorylated (p)-tau, total (t)-tau, and amyloid-β 1-42 (Aβ
METHODS METHODS
We conducted a tandem mass tag (TMT) proteomic analysis of lumbar CSF from 68 iNPH patients, sampled pre-shunt surgery. Tryptic digests of CSF samples were labelled with TMTpro reagents. The TMT multiplex samples were fractionated in 24 concatenated fractions by reversed-phase chromatography at basic pH and analysed by liquid chromatography coupled to mass spectrometry (LC-MS) on an Orbitrap Lumos mass spectrometer. The relative abundances of the identified proteins were correlated with (i) iNPH grading scale (iNPHGS) and (ii) gait speed change 1 year after surgery from baseline to identify predictors of shunt responsiveness.
RESULTS RESULTS
We identified four CSF biomarker candidates which correlated most strongly with clinical improvement on the iNPHGS and were significantly changed in shunt-responsive compared to shunt-unresponsive iNPH patients 1 year post-surgery: FABP3 (R = - 0.46, log
CONCLUSION CONCLUSIONS
FABP3, MIF, ANXA4, B3GAT2, ITGB1, YWHAG, OLFM2, TGFBI and DSG2 in CSF are promising prognostic biomarker candidates to predict shunt responsiveness in iNPH patients.

Identifiants

pubmed: 37277809
doi: 10.1186/s12987-023-00440-5
pii: 10.1186/s12987-023-00440-5
pmc: PMC10243080
doi:

Substances chimiques

Biomarkers 0
YWHAG protein, human 0
14-3-3 Proteins 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

40

Subventions

Organisme : NIH HHS
ID : #1R01AG068398-01
Pays : United States

Informations de copyright

© 2023. The Author(s).

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Auteurs

Sophia Weiner (S)

Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden. sophia.weiner@gu.se.

Antti Junkkari (A)

Department of Neurosurgery, NeuroCenter, Kuopio University Hospital and Neurosurgery, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.

Mathias Sauer (M)

Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.

Antti Luikku (A)

Department of Neurosurgery, NeuroCenter, Kuopio University Hospital and Neurosurgery, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.

Tuomas Rauramaa (T)

Department of Pathology, Kuopio University Hospital and University of Eastern Finland, Kuopio, Finland.

Tarja Kokkola (T)

Department of Neurology, Kuopio University Hospital and University of Eastern Finland, Kuopio, Finland.

Sanna-Kaisa Herukka (SK)

UK Dementia Research Institute, London, UK.

Kaj Blennow (K)

Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.

Henrik Zetterberg (H)

Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK.
UK Dementia Research Institute, London, UK.
Hong Kong Center for Neurodegenerative Diseases, Hong Kong, China.
Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.

Ville Leinonen (V)

Department of Neurosurgery, NeuroCenter, Kuopio University Hospital and Neurosurgery, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.

Johan Gobom (J)

Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.

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