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Cited by 88Multiple Sclerosis Research StudiesPeripheral Neuropathies and DisordersParkinson's Disease Mechanisms and Treatments

Cerebrospinal fluid lactate is associated with multiple sclerosis disease progression

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Albanese, Maria, Zagaglia, Sara, Landi, Doriana, Boffa, Laura, Nicoletti, Carolina G., Marciani, Maria Grazia, Mandolesi, Georgia, Marfia, Girolama A. +3 more·2016·Journal of Neuroinflammation
DOI 10.1186/s12974-016-0502-1PMC PMC4750170
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Abstract

BACKGROUND: Altered cerebrospinal fluid (CSF) levels of lactate have been described in neurodegenerative diseases and related to mitochondrial dysfunction and neuronal degeneration. We investigated the relationship between CSF lactate levels, disease severity, and biomarkers associated with neuroaxonal damage in patients with multiple sclerosis (MS). METHODS: One-hundred eighteen subjects with relapsing-remitting multiple sclerosis (RRMS) were included, along with one-hundred fifty seven matched controls. CSF levels of lactate, tau protein, and neurofilament light were detected at the time of diagnosis. Patients were followed-up for a mean of 5 years. Progression index (PI), multiple sclerosis severity scale (MSSS), and Bayesian risk estimate for multiple sclerosis (BREMS) were assessed as clinical measures of disease severity and progression. Differences between groups and correlation between CSF lactate, disease severity and CSF biomarkers of neuronal damage were explored. RESULTS: CSF lactate was higher in RRMS patients compared to controls. A negative correlation was found between lactate levels and disease duration. Patients with higher CSF lactate concentration had significantly higher PI, MSSS, and BREMS scores at long-term follow-up. Furthermore, CSF lactate correlated positively and significantly with CSF levels of both tau protein and neurofilament light protein. CONCLUSIONS: Measurement of CSF lactate may be helpful, in conjunction with other biomarkers of tissue damage, as an early predictor of disease severity in RRMS patients. A better understanding of the alterations of mitochondrial metabolic pathways associated to RRMS severity may pave the way to new therapeutic targets to contrast axonal damage and disease severity.

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  • The original ANLS has been controversially discussed but has also gained considerable experimental support by in vitro and in vivo studies.

    “While the original ANLS has been controversially discussed (Albanese et al., 2016;Bosoi & Rose, 2014;Dienel, 2017;Liguori et al., 2015;Yellen, 2018), it has also gained considerable experimental support by in vitro (Bouzier-Sore et al., 2003;Karagiannis et al., 2021) and in vivo studies (Mächler et al., 2016;Suzuki et al., 2011;Wyss et al., 2011;Zuend et al., 2020).”

    From Downregulated expression of lactate dehydrogenase in adult oligodendrocytes and its implication for the transfer of glycolysis products to axons (2024) · cites this paper as Albanese et al., 2016

    Albanese et al. is cited for the claim that the original astrocyte–neuron lactate shuttle (ANLS) has been controversially discussed; the later experimental-support clause cites other studies. The Background describes conflicting measurements of cerebrospinal-fluid lactate in multiple sclerosis, while the Discussion describes the lactate-shuttle hypothesis without saying that the hypothesis itself is controversial. Searches for ANLS and lactate-shuttle controversy found no passage supporting that attributed point. (LLM, conf=0.76)

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Sorted by citations

Authors
Albanese, M., Zagaglia, S., Landi, D., Boffa, L., Nicoletti, C. G., Marciani, M. G., Mandolesi, G., Marfia, G. A., Buttari, F., Mori, F., & Centonze, D.
Affiliations
  • University of Rome Tor Vergata (IT)
  • Fondazione Santa Lucia (IT)
Corresponding author
Centonze, Diego
ORCID
Venue
Journal of Neuroinflammation
Publisher
Springer Science and Business Media LLC
Published
2016-02-10
Volume
13
Issue
1
Pages
36-36
ISSN
1742-2094 (ISSN-L)
DOI
10.1186/s12974-016-0502-1
PMC
PMC4750170
OpenAlex
W2272462464
Cited by
88
References
3
Citations by year
2026: 10 · 2025: 10 · 2024: 15 · 2023: 7 · 2022: 3 · 2021: 8 · 2020: 8 · 2019: 9 · 2018: 4 · 2017: 8 · 2016: 5
FWCI
6.62
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Journal of Neuroinflammation (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion, other-oa)
Funders
Fondazione Italiana Sclerosi Multipla (Progetto Speciale FISM, 2012/S/2)
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Health Sciences › Medicine › Neurology › Peripheral Neuropathies and Disorders
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
Keywords
cerebrospinal fluid lactate, relapsing-remitting multiple sclerosis, disease progression, disease severity, tau protein, neurofilament light chain, axonal injury, neurodegeneration biomarkers, mitochondrial dysfunction, progression index
MeSH terms
Adult, Disability Evaluation, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Multiple Sclerosis, Neurologic Examination, Case-Control Studies, tau Proteins, Neurofilament Proteins, Disease Progression, Statistics, Nonparametric, Lactic Acid, Young Adult

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