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ORIGINAL RESEARCH article

Front. Neurosci.
Sec. Neurodegeneration
Volume 18 - 2024 | doi: 10.3389/fnins.2024.1376288

Consistent genes associated with structural changes in clinical Alzheimer's disease spectrum

Provisionally accepted
Yingqi Lu Yingqi Lu 1,2,3Xiaodong Zhang Xiaodong Zhang 1,4Liyu Hu Liyu Hu 1Qinxiu Cheng Qinxiu Cheng 1Zhang Zhewei Zhang Zhewei 1Haoran Zhang Haoran Zhang 1Zhuoran Xie Zhuoran Xie 1Yiheng Gao Yiheng Gao 1Dezhi Cao Dezhi Cao 4Shangjie Chen Shangjie Chen 2,3*Jinping Xu Jinping Xu 1*
  • 1 Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences (CAS), Shenzhen, Guangdong Province, China
  • 2 Department of Rehabilitation Medicine, Shenzhen Baoan People's Hospital, Shenzhen, Guangdong Province, China
  • 3 Department of Rehabilitation Medicine, The Second Affiliated Hospital of Shenzhen University, Shenzhen, China
  • 4 Shenzhen Children's Hospital, Shenzhen, Guangdong Province, China

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

    Previous studies showed widespread brain neurodegeneration in Alzheimer's disease (AD). However, the neurobiological and pathogenic substrates underlying these structural atrophy across AD spectrum remain largely understood. Herein, we obtained structural MRI imaging from ADNI datasets, including 83 early-stage mild cognitive impairments (EMCI), 83 late-stage mild cognitive impairments (LMCI), 83 AD, and 83 normal controls (NC), and aimed to explore structural atrophy across the full clinical AD spectrum and their genetic mechanism using gene expression data from Allen Human Brain Atlas. As a result, we identified significant volume atrophy in left thalamus, left cerebellum, and bilateral middle frontal gyrus across AD spectrum. These structural changes were positively associated with gene expression levels of ABCA7, SORCS1, SORL1, PILRA, PFDN1, PLXNA4, TRIP4, and CD2AP, whereas were negatively associated with gene expression levels of CD33, PLCG2, APOE, and ECHDC3 across clinical AD spectrum. Further gene enrichment analyses revealed that these positively associated genes were mainly involved in positive regulation of cellular protein localization and negative regulation of cellular component organization, whereas the negatively associated genes were mainly involved in positive regulation of iron transport. Overall, these results offered a better understanding of biological mechanisms underlying structural changes in prodromal and clinical AD.

    Keywords: Alzheimer's disease, Mild cognitive impairments, gray matter volume, Gene Expression, Enrichment analysis

    Received: 03 Feb 2024; Accepted: 14 Oct 2024.

    Copyright: © 2024 Lu, Zhang, Hu, Cheng, Zhewei, Zhang, Xie, Gao, Cao, Chen and Xu. 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:
    Shangjie Chen, Department of Rehabilitation Medicine, Shenzhen Baoan People's Hospital, Shenzhen, Guangdong Province, China
    Jinping Xu, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences (CAS), Shenzhen, 518055, Guangdong Province, China

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