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Peripheral level of CD33 and Alzheimer’s disease: a bidirectional two-sample Mendelian randomization study
Increased expression of CD33 in the brain has been suggested to be associated with increased amyloid plaque burden, while the peripheral level of CD33 in Alzheimer’s disease (AD) patients and its role in AD remain unclear. The current study aimed to systematically explore the bidirectional relations...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9529877/ https://www.ncbi.nlm.nih.gov/pubmed/36192375 http://dx.doi.org/10.1038/s41398-022-02205-4 |
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author | Gu, Xiaojing Dou, Meng Cao, Bei Jiang, Zheng Chen, Yongping |
author_facet | Gu, Xiaojing Dou, Meng Cao, Bei Jiang, Zheng Chen, Yongping |
author_sort | Gu, Xiaojing |
collection | PubMed |
description | Increased expression of CD33 in the brain has been suggested to be associated with increased amyloid plaque burden, while the peripheral level of CD33 in Alzheimer’s disease (AD) patients and its role in AD remain unclear. The current study aimed to systematically explore the bidirectional relationship between peripheral CD33 and AD. Genome-wide association study (GWAS) datasets of AD (N(cases): 21982; N(controls): 41944), blood CD33 mRNA level, the plasma CD33 protein level, and CD33 expression on immune-cell subtypes were obtained from GWASs conducted in the European population. Eligible IVs were extracted from the GWASs. MR estimates were calculated by inverse-variance weighting (IVW) and other sensitivity analyses. The main statistical analyses were conducted using TwoSampleMR (v.0.5.5) in R package (V.4.1.2).In the forward MR analysis (CD33 as exposure and AD as outcome), the IVW results indicated that elevated blood CD33 mRNA level (OR [95% CI] = 1.156[1.080, 1.238], p = 3.25e-05), elevated serum CD33 protein level (OR [95% CI] = 1.08 [1.031, 1.139], p = 1.6e-03) and increased CD33's expression on immune cell subtypes (p < 0.05) were all leading to a higher risk of AD. And sensitivity analyses supported these findings. While the reverse MR analysis (AD as exposure and CD33 as outcome) indicated that AD was not leading to the elevation of CD33's protein level in the blood (p > 0.05). In conclusion, our results indicated that elevated peripheral expression of CD33 was causal to the development of AD. Future studies are needed to work on developing CD33 as a biomarker and therapeutic target in AD. |
format | Online Article Text |
id | pubmed-9529877 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-95298772022-10-05 Peripheral level of CD33 and Alzheimer’s disease: a bidirectional two-sample Mendelian randomization study Gu, Xiaojing Dou, Meng Cao, Bei Jiang, Zheng Chen, Yongping Transl Psychiatry Article Increased expression of CD33 in the brain has been suggested to be associated with increased amyloid plaque burden, while the peripheral level of CD33 in Alzheimer’s disease (AD) patients and its role in AD remain unclear. The current study aimed to systematically explore the bidirectional relationship between peripheral CD33 and AD. Genome-wide association study (GWAS) datasets of AD (N(cases): 21982; N(controls): 41944), blood CD33 mRNA level, the plasma CD33 protein level, and CD33 expression on immune-cell subtypes were obtained from GWASs conducted in the European population. Eligible IVs were extracted from the GWASs. MR estimates were calculated by inverse-variance weighting (IVW) and other sensitivity analyses. The main statistical analyses were conducted using TwoSampleMR (v.0.5.5) in R package (V.4.1.2).In the forward MR analysis (CD33 as exposure and AD as outcome), the IVW results indicated that elevated blood CD33 mRNA level (OR [95% CI] = 1.156[1.080, 1.238], p = 3.25e-05), elevated serum CD33 protein level (OR [95% CI] = 1.08 [1.031, 1.139], p = 1.6e-03) and increased CD33's expression on immune cell subtypes (p < 0.05) were all leading to a higher risk of AD. And sensitivity analyses supported these findings. While the reverse MR analysis (AD as exposure and CD33 as outcome) indicated that AD was not leading to the elevation of CD33's protein level in the blood (p > 0.05). In conclusion, our results indicated that elevated peripheral expression of CD33 was causal to the development of AD. Future studies are needed to work on developing CD33 as a biomarker and therapeutic target in AD. Nature Publishing Group UK 2022-10-03 /pmc/articles/PMC9529877/ /pubmed/36192375 http://dx.doi.org/10.1038/s41398-022-02205-4 Text en © The Author(s) 2022 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Gu, Xiaojing Dou, Meng Cao, Bei Jiang, Zheng Chen, Yongping Peripheral level of CD33 and Alzheimer’s disease: a bidirectional two-sample Mendelian randomization study |
title | Peripheral level of CD33 and Alzheimer’s disease: a bidirectional two-sample Mendelian randomization study |
title_full | Peripheral level of CD33 and Alzheimer’s disease: a bidirectional two-sample Mendelian randomization study |
title_fullStr | Peripheral level of CD33 and Alzheimer’s disease: a bidirectional two-sample Mendelian randomization study |
title_full_unstemmed | Peripheral level of CD33 and Alzheimer’s disease: a bidirectional two-sample Mendelian randomization study |
title_short | Peripheral level of CD33 and Alzheimer’s disease: a bidirectional two-sample Mendelian randomization study |
title_sort | peripheral level of cd33 and alzheimer’s disease: a bidirectional two-sample mendelian randomization study |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9529877/ https://www.ncbi.nlm.nih.gov/pubmed/36192375 http://dx.doi.org/10.1038/s41398-022-02205-4 |
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