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Cerebrospinal fluid leptin in Alzheimer’s disease: relationship to plasma levels and to cerebrospinal amyloid

  • Elodie Bouaziz-Amar EMAIL logo , Jeanne Neez , Fidaa Ibrahim , Matthieu Martinet , Claire Hourregue , Julien Dumurgier , Emmanuel Cognat , Francois Mouton-Liger , Agathe Vrillon , Jacques Hugon , Claire Paquet and Matthieu Lilamand
Published/Copyright: September 1, 2025
Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 63 Issue 12

Abstract

Objectives

Dysregulation of brain leptin signaling contributes to Alzheimer’s disease (AD) pathophysiology, but plasma leptin may not accurately reflect central nervous system activity. This study examined the correlation between plasma and cerebrospinal fluid (CSF) leptin levels and their relationship with beta-amyloid (Aβ) and tau biomarkers.

Methods

Cross-sectional analysis of data from cognitively impaired patients from a tertiary memory clinic. All the patients were diagnosed using CSF AD biomarkers. CSF and plasma leptin were measured using standardized immunoassays. The correlation between plasma and CSF leptin levels was studied. CSF leptin levels were compared between patients with positive AD biomarkers (A+T+N+) and neurological controls (A−T−N−). Regression analyses were performed to study the relationship between CSF leptin and CSF amyloid and tau biomarkers, with adjustment for age, gender, body mass index (BMI) and estimated glomerular filtration rate (eGFR).

Results

Finally, 140 participants were included (age 69.8 [1.1], females=47.4 %). CSF and plasma leptin were highly correlated (r=0.79, p=<0.0001). Individuals with AD CSF profile (A+T+N+) showed lower CSF leptin concentrations than their A−T−N− counterparts (74.7 [4.7] vs. 120.9 [11.9] ng/L, p<0.01) and CSF leptin remained associated with ATN profile and more specifically with the amyloid beta ratio after adjusting for confounding factors (β=−0.60, [0.73], p<0.01).

Conclusions

CSF leptin levels strongly correlate with plasma leptin and are reduced in individuals with AD biomarker positivity. This suggests plasma leptin may reflect central leptin activity. Our findings support a link between leptin signaling and amyloid deposition in AD.

Keywords: leptin; Alzheimer’s disease; biomarker; cerebrospinal fluid; metabolic dysfonction
Corresponding author: Elodie Bouaziz-Amar, Université Paris Cité, INSERM Unit UMR S-1144, Paris, France; and Biochemistry Department, Lariboisière Hospital, 2 rue Ambroise Paré, 75010, Paris, France, E-mail:
Claire Paquet and Matthieu Lilamand share last authorship

Funding source: Institut National de la Santé et de la Recherche Médicale

Acknowledgments

Dr. Elise Dalmas of the Institut Necker-Enfants Malades (INEM), Université Paris Cité, INSERM UMR-S1151, CNRS UMR-S8253, Paris, France for her invaluable help in using the Meso Quickplex.

  1. Research ethics: This study was approved by the local Ethics Committee (Comité d’Evaluation et d’Ethique pour la Recherche Paris Nord, Institutional Review Board 00006477 ref 16-004) and the Commission Nationale Informatique et Libertés.

  2. Informed consent: Informed consent was obtained from all individuals included in this study, or their legal guardians or wards.

  3. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  4. Use of Large Language Models, AI and Machine Learning Tools: AI to improve language.

  5. Conflict of interest: The authors state no conflict of interest.

  6. Research funding: This work was supported by the French National Institute of Health and Medical Research.

  7. Data availability: The data that support the findings of this study are available from the corresponding author, EBA, upon reasonable request.

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Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/cclm-2025-0304).

Received: 2025-03-13
Accepted: 2025-08-04
Published Online: 2025-09-01
Published in Print: 2025-11-25

© 2025 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/cclm-2025-0304
Keywords for this article
leptin; Alzheimer’s disease; biomarker; cerebrospinal fluid; metabolic dysfonction

Articles in the same Issue

  1. Frontmatter
  2. Editorials
  3. Challenging the dogma: why reviewers should be allowed to use AI tools
  4. Multivariate approaches to improve the interpretation of laboratory data
  5. Review
  6. Interference of therapeutic monoclonal antibodies with electrophoresis and immunofixation of serum proteins: state of knowledge and systematic review
  7. Opinion Papers
  8. Urgent call to the European Commission to simplify and contextualize IVDR Article 5.5 for tailored and precision diagnostics
  9. The importance of laboratory medicine in the management of CKD-MBD: insights from the KDIGO 2023 controversies conference
  10. Supplementation of pyridoxal-5′-phosphate in aminotransferase reagents: a matter of patient safety
  11. HCV serology: an unfinished agenda
  12. From metabolic profiles to clinical interpretation: multivariate approaches to population-based and personalized reference intervals and reference change values
  13. Genetics and Molecular Diagnostics
  14. A multiplex allele specific PCR capillary electrophoresis (mASPCR-CE) assay for simultaneously analysis of SMN1/SMN2/NAIP copy number and SMN1 loss-of-function variants
  15. General Clinical Chemistry and Laboratory Medicine
  16. From assessment to action: experience from a quality improvement initiative integrating indicator evaluation and adverse event analysis in a clinical laboratory
  17. Evaluation of measurement uncertainty of 11 serum proteins measured by immunoturbidimetric methods according to ISO/TS 20914: a 1-year laboratory data analysis
  18. Assessing the harmonization of current total vitamin B12 measurement methods: relevance and implications
  19. The current status of serum insulin measurements and the need for standardization
  20. Method comparison of plasma and CSF GFAP immunoassays across multiple platforms
  21. Cerebrospinal fluid leptin in Alzheimer’s disease: relationship to plasma levels and to cerebrospinal amyloid
  22. Verification of the T50 Calciprotein Crystallization test: bias estimation and interferences
  23. An innovative immunoassay for accurate aldosterone quantification: overcoming low-level inaccuracy and renal dysfunction-associated interference
  24. Oral salt loading combined with postural stimulation tests for confirming and subtyping primary aldosteronism
  25. Evaluating the performance of a multiparametric IgA assay for celiac disease diagnosis
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  28. Establishment of region-, age- and sex-specific reference intervals for aldosterone and renin with sandwich chemiluminescence immunoassays
  29. Validation of a plasma GFAP immunoassay and establishment of age-related reference values: bridging analytical performance and routine implementation
  30. Comparative analysis of population-based and personalized reference intervals for biochemical markers in peri-menopausal women: population from the PALM cohort study
  31. Hematology and Coagulation
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  35. Diabetes
  36. Method comparison of diabetes mellitus associated autoantibodies in serum specimens
  37. Letters to the Editor
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  39. Response to the editorial by Karl Lackner
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  49. Association of Clinical Biochemists in Ireland Annual Conference
  50. 17th Congress of the Portuguese Society of Clinical Chemistry, Genetics and Laboratory Medicine
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