Differential proteomic profile of lumbar and ventricular cerebrospinal fluid

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Pathological 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.

CSF 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.

In 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.

The 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
TidsskriftFluids and Barriers of the CNS
Udgave nummer1
Antal sider13
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
Funding was received from the Novo Nordisk Foundation (Tandem Grant NNF17OC0024718 to NM and MJ and Grant NNF19OC0055001 to Nicolai J. Wewer Albrechtsen supporting LD, MO, and CR) and Absalonfonden (to AHS and SGH). HZ is a Wallenberg Scholar supported by Grants from the Swedish Research Council (#2018-02532), the European Research Council (#681712 and #101053962), Swedish State Support for Clinical Research (#ALFGBG-71320), the Alzheimer Drug Discovery Foundation (ADDF), USA (#201809-2016862), the AD Strategic Fund and the Alzheimer's Association (#ADSF-21-831376-C, #ADSF-21-831381-C and #ADSF-21-831377-C), the Olav Thon Foundation, the Erling-Persson Family Foundation, Stiftelsen för Gamla Tjänarinnor, Hjärnfonden, Sweden (#FO2019-0228), the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Grant Agreement No. 860197 (MIRIADE), the European Union Joint Programme—Neurodegenerative Disease Research (JPND2021-00694), and the UK Dementia Research Institute at UCL (UKDRI-1003). Novo Nordisk Foundation Center for Protein Research is supported financially by the Novo Nordisk Foundation (Grant agreement NNF14CC0001).

Funding Information:
We thank Christina Christoffersen (Department of Clinical Biochemistry, Rigshospitalet) for contributing to study design, and Christine Rasmussen and Nicolai J. Wewer Albrechtsen (NNF Center for Protein Research, University of Copenhagen) for their time designing, planning, preparing and interpreting the proteomic analysis and we also acknowledge the Clinical Proteomic Group at the NNF Center for Protein Research, University of Copenhagen, in particular Matthias Mann. Further, we thank Cecilie Holm Rasmussen and Marlene Møller from Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen for their help with the porcine samples and Naomi Wakabayashi, the Memory Clinic, Rigshospitalet, for help with collecting patient samples.

Publisher Copyright:
© 2023, The Author(s).

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