Differential proteomic profile of lumbar and ventricular cerebrospinal fluid

Abstract

Background 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. Methods 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. Results 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. Conclusions 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.

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

“…CSF is produced in the brain ventricles and circulates through the brain and spinal cord in a continuous flow (Czarniak et al., 2023 ). This flow establishes a rostro‐caudal gradient, with lower levels of some brain proteins (e.g., S‐100β, total or phosphorylated Tau), but higher levels of others (e.g., neurofilament, amyloid‐β40 or β42) in the lumbar region relative to the brain (Jingami et al., 2019 ; Rostgaard et al., 2023 ). Hence, collection site (e.g., lumbar/spinal canal vs. brain) and volume may affect CSF composition (Cameron et al., 2019 ; Teunissen et al., 2009 ).…”

Day–night fluctuations in choroid plexus transcriptomics and cerebrospinal fluid metabolomics

“…As such, these metabolites are highly likely to be present within human CSF. Human CSF is, in addition, usually sampled from the lumbar region and not from the ventricular compartment as in the present study, which influences proteomic composition ( 39 ) and therefore possibly also metabolite composition. CSF collected in the light phase versus that of the dark phase revealed differential abundance of 22% of the CSF metabolites (19 of the included 86 metabolites).…”

Cerebrospinal fluid flushing as a means of neuroprotection

“…CSF flow oscillations can differ significantly from person to person, and even within a given individual as CSF flow reverts from caudal to cranial during diastole ( Klostranec et al, 2021 ; Vijayakrishnan Nair et al, 2022 ). The dynamic and bidirectional nature of CSF flow is one explanation for why the protein content of ventricular CSF is different from that obtained from the lumbar region ( Puy et al, 2016 ; Rostgaard et al, 2023 ). Hence, the location of CSF sampling is important and cannot be assumed to be identical for different locations of CSF fluid.…”