Unraveling the mechanisms of NK cell dysfunction in aging and Alzheimer's disease : insights from GWAS and single-cell transcriptomics
Copyright © 2024 Li, Zhang, You, Huang, Wu, Liang, Weng, Pan, Huang, Huang, Yang, Lu, Li, Yan, Liu and Deng..
Background: Aging is an important factor in the development of Alzheimer's disease (AD). The senescent cells can be recognized and removed by NK cells. However, NK cell function is gradually inactivated with age. Therefore, this study used senescence as an entry point to investigate how NK cells affect AD.
Methods: The study validated the correlation between cognition and aging through a prospective cohort of the National Health and Nutrition Examination Survey database. A cellular trajectory analysis of the aging population was performed using single-cell nuclear transcriptome sequencing data from patients with AD and different ages. The genome-wide association study (GWAS) cohort of AD patients was used as the outcome event, and the expression quantitative trait locus was used as an instrumental variable. Causal associations between genes and AD were analyzed by bidirectional Mendelian randomization (MR) and co-localization. Finally, clinical cohorts were constructed to validate the expression of key genes.
Results: A correlation between cognition and aging was demonstrated using 2,171 older adults over 60 years of age. Gene regulation analysis revealed that most of the highly active transcription factors were concentrated in the NK cell subpopulation of AD. NK cell trajectories were constructed for different age populations. MR and co-localization analyses revealed that CHD6 may be one of the factors influencing AD.
Conclusion: We explored different levels of AD and aging from population cohorts, single-cell data, and GWAS cohorts and found that there may be some correlations of NK cells between aging and AD. It also provides some basis for potential causation.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
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| Enthalten in: |
Frontiers in immunology - 15(2024) vom: 11., Seite 1360687 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Li, Jinwei [VerfasserIn] |
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| Links: |
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| Themen: |
AD |
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| Anmerkungen: |
Date Completed 12.03.2024 Date Revised 15.04.2024 published: Electronic-eCollection Citation Status MEDLINE |
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| doi: |
10.3389/fimmu.2024.1360687 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369542487 |
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| 100 | 1 | |a Li, Jinwei |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Unraveling the mechanisms of NK cell dysfunction in aging and Alzheimer's disease |b insights from GWAS and single-cell transcriptomics |
| 264 | 1 | |c 2024 | |
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| 500 | |a Date Completed 12.03.2024 | ||
| 500 | |a Date Revised 15.04.2024 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2024 Li, Zhang, You, Huang, Wu, Liang, Weng, Pan, Huang, Huang, Yang, Lu, Li, Yan, Liu and Deng. | ||
| 520 | |a Background: Aging is an important factor in the development of Alzheimer's disease (AD). The senescent cells can be recognized and removed by NK cells. However, NK cell function is gradually inactivated with age. Therefore, this study used senescence as an entry point to investigate how NK cells affect AD | ||
| 520 | |a Methods: The study validated the correlation between cognition and aging through a prospective cohort of the National Health and Nutrition Examination Survey database. A cellular trajectory analysis of the aging population was performed using single-cell nuclear transcriptome sequencing data from patients with AD and different ages. The genome-wide association study (GWAS) cohort of AD patients was used as the outcome event, and the expression quantitative trait locus was used as an instrumental variable. Causal associations between genes and AD were analyzed by bidirectional Mendelian randomization (MR) and co-localization. Finally, clinical cohorts were constructed to validate the expression of key genes | ||
| 520 | |a Results: A correlation between cognition and aging was demonstrated using 2,171 older adults over 60 years of age. Gene regulation analysis revealed that most of the highly active transcription factors were concentrated in the NK cell subpopulation of AD. NK cell trajectories were constructed for different age populations. MR and co-localization analyses revealed that CHD6 may be one of the factors influencing AD | ||
| 520 | |a Conclusion: We explored different levels of AD and aging from population cohorts, single-cell data, and GWAS cohorts and found that there may be some correlations of NK cells between aging and AD. It also provides some basis for potential causation | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a AD | |
| 650 | 4 | |a Mendelian randomization | |
| 650 | 4 | |a NHANES | |
| 650 | 4 | |a ScRNA-seq | |
| 650 | 4 | |a aging | |
| 650 | 7 | |a CHD6 protein, human |2 NLM | |
| 650 | 7 | |a DNA Helicases |2 NLM | |
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| 650 | 7 | |a Nerve Tissue Proteins |2 NLM | |
| 700 | 1 | |a Zhang, Yang |e verfasserin |4 aut | |
| 700 | 1 | |a You, Yanwei |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Zhiwei |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Liya |e verfasserin |4 aut | |
| 700 | 1 | |a Liang, Cong |e verfasserin |4 aut | |
| 700 | 1 | |a Weng, Baohui |e verfasserin |4 aut | |
| 700 | 1 | |a Pan, Liya |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Yushen |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Mengqi |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Mengting |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Rui |e verfasserin |4 aut | |
| 700 | 1 | |a Yan, Xianlei |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Quan |e verfasserin |4 aut | |
| 700 | 1 | |a Deng, Shan |e verfasserin |4 aut | |
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