Cerebrospinal fluid leptin in Alzheimer’s disease: relationship to plasma levels and to cerebrospinal amyloid
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Elodie Bouaziz-Amar
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Jeanne Neez
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.
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.
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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.
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Informed consent: Informed consent was obtained from all individuals included in this study, or their legal guardians or wards.
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Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
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Use of Large Language Models, AI and Machine Learning Tools: AI to improve language.
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Conflict of interest: The authors state no conflict of interest.
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Research funding: This work was supported by the French National Institute of Health and Medical Research.
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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
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