Abstract
Introduction
Alzheimer’s disease (AD) is characterized by decreased cerebrospinal fluid (CSF) Aβ42 and Aβ42/Aβ40 ratio. Aβ peptides can now be measured also in plasma and are promising peripheral biomarkers for AD. We evaluated the relationships of plasma Aβ species with their CSF counterparts, kidney function, and serum/CSF albumin ratio (Q-Alb) in AD patients.
Materials and methods
We measured plasma Aβ42 and Aβ40, as well as CSF AD biomarkers, with the fully automated Lumipulse platform in a cohort of N = 30 patients with clinical and neurochemical diagnosis of AD.
Results
The two plasma Aβ peptides correlated strongly with each other (r = 0.7449), as did the corresponding CSF biomarkers (r = 0.7670). On the contrary, the positive correlations of plasma Aβ42, Aβ40, and Aβ42/Aβ40 ratio with their CSF counterparts and the negative correlation of plasma Aβ42/Aβ40 ratio with CSF P-tau181 were not statistically significant. Plasma levels of both Aβ species negatively correlated with estimated glomerular filtration rate (eGFR) (Aβ42: r = -0.4138; Aβ40: r = -0.6015), but plasma Aβ42/Aβ40 ratio did not. Q-Alb did not correlate with any plasma Aβ parameter.
Discussion
Plasma Aβ42 and Aβ40 are critically influenced by kidney function; however, their ratio is advantageously spared from this effect. The lack of significant correlations between plasma Aβ species and their CSF counterparts is probably mainly due to small sample size and inclusion of only Aβ + individuals. Q-Alb is not a major determinant of plasma Aβ concentrations, highlighting the uncertainties about mechanisms of Aβ transfer between CNS and periphery.
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Data availability
Data will be made available upon reasonable request.
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Acknowledgements
The authors are thankful to patients and their caregivers. The authors also thank healthcare professionals involved in patient care and laboratory personnel. The reagents for plasma Aβ measurements were kindly provided by Fujirebio Europe N.V.
Funding
The work was financially supported by the Italian Ministry of Health.
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Contributions
All authors have made substantial contributions to data collection and/or interpretation. The study was designed by F.V. Statistical analysis was performed by F.V. The manuscript was written by F.V. and critically revised by N.T. and V.S. All authors have read the final version of the manuscript and agree on it.
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Ethical approval
The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Ethics Committee of IRCCS Istituto Auxologico Italiano (code 2021_05_18_04).
Informed consent
Informed consent was obtained from all subjects involved in the study.
Conflict of interest
A.P. is an employee of Fujirebio Europe N.V. and provided technical assistance for plasma Aβ measurement; Fujirebio Europe N.V. did not influence to any extent analysis and interpretation of data. B.P. received compensation for consulting services and/or speaking activities from Liquidweb S.r.l. She is an Associate Editor for Frontiers in Neuroscience. N.T. received compensation for consulting services from Amylyx Pharmaceuticals and Zambon Biotech SA. He is an Associate Editor for Frontiers in Aging Neuroscience. V.S. received compensation for consulting services and/or speaking activities from AveXis, Cytokinetics, Italfarmaco, Liquidweb S.r.l., Novartis Pharma AG, and Zambon, and receives or has received research support from the Italian Ministry of Health, AriSLA, and E-Rare Joint Transnational Call. He is a member of the Editorial Boards of Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, European Neurology, American Journal of Neurodegenerative Disease, Frontiers in Neurology, and Exploration of Neuroprotective Therapy. The other authors have no relevant competing interests.
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Verde, F., Milone, I., Dubini, A. et al. Influence of kidney function and CSF/serum albumin ratio on plasma Aβ42 and Aβ40 levels measured on a fully automated platform in patients with Alzheimer’s disease. Neurol Sci 44, 3287–3290 (2023). https://doi.org/10.1007/s10072-023-06882-x
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DOI: https://doi.org/10.1007/s10072-023-06882-x