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Unraveling the mechanisms of NK cell dysfunction in aging and Alzheimer's disease: insights from GWAS and single-cell transcriptomics
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....
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Published in: | Frontiers in immunology 2024, Vol.15, p.1360687 |
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creator | Li, Jinwei Zhang, Yang You, Yanwei Huang, Zhiwei Wu, Liya Liang, Cong Weng, Baohui Pan, Liya Huang, Yan Huang, Yushen Yang, Mengqi Lu, Mengting Li, Rui Yan, Xianlei Liu, Quan Deng, Shan |
description | 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.
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.
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
may be one of the factors influencing AD.
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. |
doi_str_mv | 10.3389/fimmu.2024.1360687 |
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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.
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
may be one of the factors influencing AD.
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.</description><identifier>ISSN: 1664-3224</identifier><identifier>EISSN: 1664-3224</identifier><identifier>DOI: 10.3389/fimmu.2024.1360687</identifier><identifier>PMID: 38464521</identifier><language>eng</language><publisher>Switzerland: Frontiers Media S.A</publisher><subject>Aged ; aging ; Aging - genetics ; Alzheimer Disease - genetics ; DNA Helicases ; Gene Expression Profiling ; Genome-Wide Association Study ; Humans ; Killer Cells, Natural ; Mendelian randomization ; Middle Aged ; Nerve Tissue Proteins ; NHANES ; Nutrition Surveys ; Prospective Studies ; ScRNA-seq</subject><ispartof>Frontiers in immunology, 2024, Vol.15, p.1360687</ispartof><rights>Copyright © 2024 Li, Zhang, You, Huang, Wu, Liang, Weng, Pan, Huang, Huang, Yang, Lu, Li, Yan, Liu and Deng.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c364t-66904ecb7ff6266ffbcb830acfe7173327841ab34b3795f3965f6fd130378523</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,4024,27923,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38464521$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Jinwei</creatorcontrib><creatorcontrib>Zhang, Yang</creatorcontrib><creatorcontrib>You, Yanwei</creatorcontrib><creatorcontrib>Huang, Zhiwei</creatorcontrib><creatorcontrib>Wu, Liya</creatorcontrib><creatorcontrib>Liang, Cong</creatorcontrib><creatorcontrib>Weng, Baohui</creatorcontrib><creatorcontrib>Pan, Liya</creatorcontrib><creatorcontrib>Huang, Yan</creatorcontrib><creatorcontrib>Huang, Yushen</creatorcontrib><creatorcontrib>Yang, Mengqi</creatorcontrib><creatorcontrib>Lu, Mengting</creatorcontrib><creatorcontrib>Li, Rui</creatorcontrib><creatorcontrib>Yan, Xianlei</creatorcontrib><creatorcontrib>Liu, Quan</creatorcontrib><creatorcontrib>Deng, Shan</creatorcontrib><title>Unraveling the mechanisms of NK cell dysfunction in aging and Alzheimer's disease: insights from GWAS and single-cell transcriptomics</title><title>Frontiers in immunology</title><addtitle>Front Immunol</addtitle><description>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.
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.
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
may be one of the factors influencing AD.
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.</description><subject>Aged</subject><subject>aging</subject><subject>Aging - genetics</subject><subject>Alzheimer Disease - genetics</subject><subject>DNA Helicases</subject><subject>Gene Expression Profiling</subject><subject>Genome-Wide Association Study</subject><subject>Humans</subject><subject>Killer Cells, Natural</subject><subject>Mendelian randomization</subject><subject>Middle Aged</subject><subject>Nerve Tissue Proteins</subject><subject>NHANES</subject><subject>Nutrition Surveys</subject><subject>Prospective Studies</subject><subject>ScRNA-seq</subject><issn>1664-3224</issn><issn>1664-3224</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>DOA</sourceid><recordid>eNpNkU1v1DAQhiMEolXpH-CAfINLltjjOAm3VVVKRQUHijhatjPedRXHiydBKnf-N9kPKnwZa_S8j2W9RfGaVyuAtnvvQ4zzSlRCrjioSrXNs-KcKyVLEEI-_-9-VlwSPVTLkR0A1C-LM2ilkrXg58Wf72M2v3AI44ZNW2QR3daMgSKx5NmXz8zhMLD-kfw8uimkkYWRmc0eN2PP1sPvLYaI-S2xPhAawg8LQWGznYj5nCK7-bH-dmBpCQ1YHoRTNiO5HHZTisHRq-KFNwPh5WleFPcfr--vPpV3X29ur9Z3pQMlp1KprpLobOO9Ekp5b51toTLOY8MbANG0khsL0kLT1R46VXvlew4VNG0t4KK4PWr7ZB70Lodo8qNOJujDIuWNNnkKbkDdgW3R-haE6aVHbjlYVH1bKZQG0Cyud0fXLqefM9KkY6D938yIaSYturoWSgoBCyqOqMuJKKN_eppXel-mPpSp92XqU5lL6M3JP9uI_VPkX3XwF4ptnOs</recordid><startdate>2024</startdate><enddate>2024</enddate><creator>Li, Jinwei</creator><creator>Zhang, Yang</creator><creator>You, Yanwei</creator><creator>Huang, Zhiwei</creator><creator>Wu, Liya</creator><creator>Liang, Cong</creator><creator>Weng, Baohui</creator><creator>Pan, Liya</creator><creator>Huang, Yan</creator><creator>Huang, Yushen</creator><creator>Yang, Mengqi</creator><creator>Lu, Mengting</creator><creator>Li, Rui</creator><creator>Yan, Xianlei</creator><creator>Liu, Quan</creator><creator>Deng, Shan</creator><general>Frontiers Media S.A</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>DOA</scope></search><sort><creationdate>2024</creationdate><title>Unraveling the mechanisms of NK cell dysfunction in aging and Alzheimer's disease: insights from GWAS and single-cell transcriptomics</title><author>Li, Jinwei ; Zhang, Yang ; You, Yanwei ; Huang, Zhiwei ; Wu, Liya ; Liang, Cong ; Weng, Baohui ; Pan, Liya ; Huang, Yan ; Huang, Yushen ; Yang, Mengqi ; Lu, Mengting ; Li, Rui ; Yan, Xianlei ; Liu, Quan ; Deng, Shan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c364t-66904ecb7ff6266ffbcb830acfe7173327841ab34b3795f3965f6fd130378523</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Aged</topic><topic>aging</topic><topic>Aging - genetics</topic><topic>Alzheimer Disease - genetics</topic><topic>DNA Helicases</topic><topic>Gene Expression Profiling</topic><topic>Genome-Wide Association Study</topic><topic>Humans</topic><topic>Killer Cells, Natural</topic><topic>Mendelian randomization</topic><topic>Middle Aged</topic><topic>Nerve Tissue Proteins</topic><topic>NHANES</topic><topic>Nutrition Surveys</topic><topic>Prospective Studies</topic><topic>ScRNA-seq</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Jinwei</creatorcontrib><creatorcontrib>Zhang, Yang</creatorcontrib><creatorcontrib>You, Yanwei</creatorcontrib><creatorcontrib>Huang, Zhiwei</creatorcontrib><creatorcontrib>Wu, Liya</creatorcontrib><creatorcontrib>Liang, Cong</creatorcontrib><creatorcontrib>Weng, Baohui</creatorcontrib><creatorcontrib>Pan, Liya</creatorcontrib><creatorcontrib>Huang, Yan</creatorcontrib><creatorcontrib>Huang, Yushen</creatorcontrib><creatorcontrib>Yang, Mengqi</creatorcontrib><creatorcontrib>Lu, Mengting</creatorcontrib><creatorcontrib>Li, Rui</creatorcontrib><creatorcontrib>Yan, Xianlei</creatorcontrib><creatorcontrib>Liu, Quan</creatorcontrib><creatorcontrib>Deng, Shan</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Frontiers in immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Jinwei</au><au>Zhang, Yang</au><au>You, Yanwei</au><au>Huang, Zhiwei</au><au>Wu, Liya</au><au>Liang, Cong</au><au>Weng, Baohui</au><au>Pan, Liya</au><au>Huang, Yan</au><au>Huang, Yushen</au><au>Yang, Mengqi</au><au>Lu, Mengting</au><au>Li, Rui</au><au>Yan, Xianlei</au><au>Liu, Quan</au><au>Deng, Shan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Unraveling the mechanisms of NK cell dysfunction in aging and Alzheimer's disease: insights from GWAS and single-cell transcriptomics</atitle><jtitle>Frontiers in immunology</jtitle><addtitle>Front Immunol</addtitle><date>2024</date><risdate>2024</risdate><volume>15</volume><spage>1360687</spage><pages>1360687-</pages><issn>1664-3224</issn><eissn>1664-3224</eissn><abstract>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.
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.
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
may be one of the factors influencing AD.
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.</abstract><cop>Switzerland</cop><pub>Frontiers Media S.A</pub><pmid>38464521</pmid><doi>10.3389/fimmu.2024.1360687</doi><oa>free_for_read</oa></addata></record> |
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subjects | Aged aging Aging - genetics Alzheimer Disease - genetics DNA Helicases Gene Expression Profiling Genome-Wide Association Study Humans Killer Cells, Natural Mendelian randomization Middle Aged Nerve Tissue Proteins NHANES Nutrition Surveys Prospective Studies ScRNA-seq |
title | Unraveling the mechanisms of NK cell dysfunction in aging and Alzheimer's disease: insights from GWAS and single-cell transcriptomics |
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