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ORIGINAL RESEARCH article

Front. Aging Neurosci.
Sec. Alzheimer's Disease and Related Dementias
Volume 16 - 2024 | doi: 10.3389/fnagi.2024.1477327
This article is part of the Research Topic A comprehensive look at biomarkers in neurodegenerative diseases: from early diagnosis to treatment response assessment View all 15 articles

Identification of altered immune cell types and molecular mechanisms in Alzheimer's disease progression by single-cell RNA sequencing

Provisionally accepted
Hua Lin Hua Lin 1*Li Su Li Su 2Daniel Mao Daniel Mao 3*Grace Yang Grace Yang 4*Qi Huang Qi Huang 1*Yating Lan Yating Lan 1*Jingyi Zeng Jingyi Zeng 1*Wenyi Song Wenyi Song 1*Guining Liang Guining Liang 1*Qingyan Wei Qingyan Wei 1*Chanhua Zou Chanhua Zou 5*Rongjie Li Rongjie Li 6*Donghua Zou Donghua Zou 1*
  • 1 The Second Affiliated Hospital of GuangXi Medical University, Nanning, China
  • 2 The Affifiliated Hospital of Youjiang Medical University for Nationalities, Baise, China
  • 3 The Pennsylvania State University (PSU), University Park, Pennsylvania, United States
  • 4 State College Area High School, State College, Pennsylvania, United States
  • 5 Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Region, China
  • 6 The Fifth Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Region, China

The final, formatted version of the article will be published soon.

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by gradual loss of cognitive function. Understanding the molecular mechanisms underlying AD is crucial for developing effective therapies. Data from peripheral blood in single-cell RNA sequencing (scRNAseq) in the GSE181279 dataset and gene chips in the GSE63060 and GSE63061 datasets were collected and analyzed to identify immune cell types and differentially expressed genes. Cell communication, pseudotime trajectory, enrichment analysis, co-expression network, and short timeseries expression miner were analyzed to identify disease-specific molecular and cellular mechanisms. We identified eight cell types (B cells, monocytes, natural killer cells, gamma-delta T cells, CD8+ T cells, Tem/Temra cytotoxic T cells, Tem/Trm cytotoxic T cells, and mucosalassociated invariant T cells) using scRNA-seq. AD samples were enriched in monocytes, CD8+ T cells, Tem/Temra cytotoxic T cells, and Tem/Trm cytotoxic T cells, whereas samples from healthy controls were enriched in natural killer and mucosal-associated invariant T cells. Five co-expression modules that were identified through weighted gene correlation network analysis were enriched in immune-inflammatory pathways. Candidate genes with higher area under the receiver operating characteristic curve values were screened, and the expression trend of Ubiquitin-Fold Modifier Conjugating Enzyme 1 (UFC1) gradually decreased from healthy controls to mild cognitive impairment and then to AD. Our study suggests that peripheral immune cells may be a potential therapeutic target for AD. Candidate genes, particularly, UFC1, may serve as potential biomarkers for progression of AD.

    Keywords: Alzheimer's disease, immune cells, single-cell RNA sequencing, UFC1, Monocytes, Tlymphocytes

    Received: 07 Aug 2024; Accepted: 24 Oct 2024.

    Copyright: © 2024 Lin, Su, Mao, Yang, Huang, Lan, Zeng, Song, Liang, Wei, Zou, Li and Zou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Hua Lin, The Second Affiliated Hospital of GuangXi Medical University, Nanning, China
    Daniel Mao, The Pennsylvania State University (PSU), University Park, 16802, Pennsylvania, United States
    Grace Yang, State College Area High School, State College, 16801, Pennsylvania, United States
    Qi Huang, The Second Affiliated Hospital of GuangXi Medical University, Nanning, China
    Yating Lan, The Second Affiliated Hospital of GuangXi Medical University, Nanning, China
    Jingyi Zeng, The Second Affiliated Hospital of GuangXi Medical University, Nanning, China
    Wenyi Song, The Second Affiliated Hospital of GuangXi Medical University, Nanning, China
    Guining Liang, The Second Affiliated Hospital of GuangXi Medical University, Nanning, China
    Qingyan Wei, The Second Affiliated Hospital of GuangXi Medical University, Nanning, China
    Chanhua Zou, Guangxi Medical University Cancer Hospital, Nanning, 530021, Guangxi Zhuang Region, China
    Rongjie Li, The Fifth Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Region, China
    Donghua Zou, The Second Affiliated Hospital of GuangXi Medical University, Nanning, China

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