Author:
Rostgaard Nina,Olsen Markus Harboe,Ottenheijm Maud,Drici Lylia,Simonsen Anja Hviid,Plomgaard Peter,Gredal Hanne,Poulsen Helle Harding,Zetterberg Henrik,Blennow Kaj,Hasselbalch Steen Gregers,MacAulay Nanna,Juhler Marianne
Abstract
AbstractBackgroundPathological cerebral conditions may manifest in altered composition of the cerebrospinal fluid (CSF). Although diagnostic CSF analysis seeks to establish pathological disturbances in the brain proper, CSF is generally sampled from the lumbar compartment for reasons of technical ease and ethical considerations. We here aimed to compare the molecular composition of CSF obtained from the ventricular versus the lumbar CSF compartments to establish a relevance for employing lumbar CSF as a proxy for the CSF bathing the brain tissue.MethodsCSF was collected from 46 patients with idiopathic normal pressure hydrocephalus (iNPH) patients during their diagnostic workup (lumbar samples) and in connection with their subsequent CSF diversion shunt surgery (ventricular samples). The mass-spectrometry-based proteomic profile was determined in these samples and in addition, selected biomarkers were quantified with ELISA (S100B, neurofilament light (NfL), amyloid-β (Aβ40, Aβ42), and total tau (T-tau) and phosphorylated tau (P-tau) forms). The latter analysis was extended to include paired porcine samples obtained from the lumbar compartment and the cerebromedullary cistern closely related to the ventricles.ResultsIn total 1231 proteins were detected in the human CSF. Of these, 216 distributed equally in the two CSF compartments, whereas 22 were preferentially (or solely) present in the ventricular CSF and four in the lumbar CSF. The selected biomarkers of neurodegeneration and Alzheimer’s disease displayed differential distribution, some with higher (S100B, T-tau, and P-tau) and some with lower (NfL, Aβ40, Aβ42) levels in the ventricular compartment. In the porcine samples, all biomarkers were most abundant in the lumbar CSF.ConclusionsThe overall proteomic profile differs between the ventricular and the lumbar CSF compartments, and so does the distribution of clinically employed biomarkers. However, for a range of CSF proteins and biomarkers, one can reliably employ lumbar CSF as a proxy for ventricular CSF if or a lumbar/cranial index for the particular molecule has been established. It is therefore important to verify the compartmental preference of the proteins or biomarkers of interest prior to extrapolating from lumbar CSF to that of the ventricular fluid bordering the brain.
Funder
Novo Nordisk Fonden
Novo Nordisk Fonden,Denmark
Absalonfonden
Swedish Research Counsil
European Research Council
European Research Council,European Union
Swedish State Support for Clinical Research
Alzheimer's Drug Discovery Foundation
AD Strategic Fund and the Alzheimer's Association
Olav Thon Stiftelsen
Familjen Erling-Perssons Stiftelse
Stiftelsen för Gamla Tjänarinnor
Hjärnfonden
European Union’s Horizon 2020 research and innovation programme
European Union Joint Programme – Neurodegenerative Disease Research
UK Dementia Research Institute at UCL
Publisher
Springer Science and Business Media LLC
Subject
Cellular and Molecular Neuroscience,Developmental Neuroscience,Neurology,General Medicine
Cited by
8 articles.
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