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Plasma and cerebrospinal fluid cholesterol esterification is hampered in Alzheimer’s disease
OBJECTIVE: The purpose of this study was to evaluate cholesterol esterification and HDL subclasses in plasma and cerebrospinal fluid (CSF) of Alzheimer’s disease (AD) patients. METHODS: The study enrolled 70 AD patients and 74 cognitively normal controls comparable for age and sex. Lipoprotein profi...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10199596/ https://www.ncbi.nlm.nih.gov/pubmed/37210544 http://dx.doi.org/10.1186/s13195-023-01241-6 |
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author | Turri, Marta Conti, Elisa Pavanello, Chiara Gastoldi, Francesco Palumbo, Marcella Bernini, Franco Aprea, Vittoria Re, Francesca Barbiroli, Alberto Emide, Davide Galimberti, Daniela Tremolizzo, Lucio Zimetti, Francesca Calabresi, Laura |
author_facet | Turri, Marta Conti, Elisa Pavanello, Chiara Gastoldi, Francesco Palumbo, Marcella Bernini, Franco Aprea, Vittoria Re, Francesca Barbiroli, Alberto Emide, Davide Galimberti, Daniela Tremolizzo, Lucio Zimetti, Francesca Calabresi, Laura |
author_sort | Turri, Marta |
collection | PubMed |
description | OBJECTIVE: The purpose of this study was to evaluate cholesterol esterification and HDL subclasses in plasma and cerebrospinal fluid (CSF) of Alzheimer’s disease (AD) patients. METHODS: The study enrolled 70 AD patients and 74 cognitively normal controls comparable for age and sex. Lipoprotein profile, cholesterol esterification, and cholesterol efflux capacity (CEC) were evaluated in plasma and CSF. RESULTS: AD patients have normal plasma lipids but significantly reduced unesterified cholesterol and unesterified/total cholesterol ratio. Lecithin:cholesterol acyltransferase (LCAT) activity and cholesterol esterification rate (CER), two measures of the efficiency of the esterification process, were reduced by 29% and 16%, respectively, in the plasma of AD patients. Plasma HDL subclass distribution in AD patients was comparable to that of controls but the content of small discoidal preβ-HDL particles was significantly reduced. In agreement with the reduced preβ-HDL particles, cholesterol efflux capacity mediated by the transporters ABCA1 and ABCG1 was reduced in AD patients’ plasma. The CSF unesterified to total cholesterol ratio was increased in AD patients, and CSF CER and CEC from astrocytes were significantly reduced in AD patients. In the AD group, a significant positive correlation was observed between plasma unesterified cholesterol and unesterified/total cholesterol ratio with Aβ(1-42) CSF content. CONCLUSION: Taken together our data indicate that cholesterol esterification is hampered in plasma and CSF of AD patients and that plasma cholesterol esterification biomarkers (unesterified cholesterol and unesterified/total cholesterol ratio) are significantly associated to disease biomarkers (i.e., CSF Aβ(1-42)). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13195-023-01241-6. |
format | Online Article Text |
id | pubmed-10199596 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-101995962023-05-21 Plasma and cerebrospinal fluid cholesterol esterification is hampered in Alzheimer’s disease Turri, Marta Conti, Elisa Pavanello, Chiara Gastoldi, Francesco Palumbo, Marcella Bernini, Franco Aprea, Vittoria Re, Francesca Barbiroli, Alberto Emide, Davide Galimberti, Daniela Tremolizzo, Lucio Zimetti, Francesca Calabresi, Laura Alzheimers Res Ther Research OBJECTIVE: The purpose of this study was to evaluate cholesterol esterification and HDL subclasses in plasma and cerebrospinal fluid (CSF) of Alzheimer’s disease (AD) patients. METHODS: The study enrolled 70 AD patients and 74 cognitively normal controls comparable for age and sex. Lipoprotein profile, cholesterol esterification, and cholesterol efflux capacity (CEC) were evaluated in plasma and CSF. RESULTS: AD patients have normal plasma lipids but significantly reduced unesterified cholesterol and unesterified/total cholesterol ratio. Lecithin:cholesterol acyltransferase (LCAT) activity and cholesterol esterification rate (CER), two measures of the efficiency of the esterification process, were reduced by 29% and 16%, respectively, in the plasma of AD patients. Plasma HDL subclass distribution in AD patients was comparable to that of controls but the content of small discoidal preβ-HDL particles was significantly reduced. In agreement with the reduced preβ-HDL particles, cholesterol efflux capacity mediated by the transporters ABCA1 and ABCG1 was reduced in AD patients’ plasma. The CSF unesterified to total cholesterol ratio was increased in AD patients, and CSF CER and CEC from astrocytes were significantly reduced in AD patients. In the AD group, a significant positive correlation was observed between plasma unesterified cholesterol and unesterified/total cholesterol ratio with Aβ(1-42) CSF content. CONCLUSION: Taken together our data indicate that cholesterol esterification is hampered in plasma and CSF of AD patients and that plasma cholesterol esterification biomarkers (unesterified cholesterol and unesterified/total cholesterol ratio) are significantly associated to disease biomarkers (i.e., CSF Aβ(1-42)). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13195-023-01241-6. BioMed Central 2023-05-20 /pmc/articles/PMC10199596/ /pubmed/37210544 http://dx.doi.org/10.1186/s13195-023-01241-6 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Turri, Marta Conti, Elisa Pavanello, Chiara Gastoldi, Francesco Palumbo, Marcella Bernini, Franco Aprea, Vittoria Re, Francesca Barbiroli, Alberto Emide, Davide Galimberti, Daniela Tremolizzo, Lucio Zimetti, Francesca Calabresi, Laura Plasma and cerebrospinal fluid cholesterol esterification is hampered in Alzheimer’s disease |
title | Plasma and cerebrospinal fluid cholesterol esterification is hampered in Alzheimer’s disease |
title_full | Plasma and cerebrospinal fluid cholesterol esterification is hampered in Alzheimer’s disease |
title_fullStr | Plasma and cerebrospinal fluid cholesterol esterification is hampered in Alzheimer’s disease |
title_full_unstemmed | Plasma and cerebrospinal fluid cholesterol esterification is hampered in Alzheimer’s disease |
title_short | Plasma and cerebrospinal fluid cholesterol esterification is hampered in Alzheimer’s disease |
title_sort | plasma and cerebrospinal fluid cholesterol esterification is hampered in alzheimer’s disease |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10199596/ https://www.ncbi.nlm.nih.gov/pubmed/37210544 http://dx.doi.org/10.1186/s13195-023-01241-6 |
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