Neural Regeneration Research ›› 2026, Vol. 21 ›› Issue (8): 3769-3778.doi: 10.4103/NRR.NRR-D-25-00493

Previous Articles     Next Articles

Integrated multi-omics reveal potential therapeutic targets for Alzheimer's disease

Hongli Li1, #, Jin Kang2, #, Zilin Liang3, Xiaowei Wang4, Lemei Zhu1, 5, Hanfen Tang6, *, Weijun Peng1, 5, *   

  1. 1Department of Integrated Traditional Chinese & Western Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China; 
    2Department of Rheumatology and Immunology, The Second Xiangya Hospital of Central South University, Changsha, Hunan Province, China; 
    3School of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan Province, China; 
    4Department of Pathology, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China; 
    5Academician Workstation, Changsha Medical University, Changsha, Hunan Province, China; 
    6Department of Nutrition, Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China
  • Online:2026-08-18 Published:2026-04-27
  • Contact: Weijun Peng, PhD, pengweijun87@csu.edu.cn; Hanfen Tang, PhD, tanghanfen0826@csu.edu.cn.
  • Supported by:
    This study was financially supported by the National Natural Science Foundation of China, No. 82374552 (to WP); the Natural Science Foundation of Hunan Province, Nos. 2024JJ2086, 2024JJ6597 (to JK); the Science and Technology Innovation Program of Hunan Province, No. 2022RC1220 (to WP); and Support Plan for High-Level Health and Medical Talents in Hunan Province, No. 20240304076 (to WP).

PDF

2

Abstract:

Because the pathogenesis of Alzheimer’s disease is multifactorial and complex, integrated multi-level omics analysis is essential to comprehensively elucidate its molecular alterations. We therefore utilized the well-established amyloid precursor protein/presenilin 1 mouse model to carry out an integrated multi-omics study using transcriptomic, proteomic, N6- methyladenosine epitranscriptomic, and phosphoproteomic analyses. The results revealed substantial molecular alterations across multiple biological dimensions and the alteration in the expression of several key genes, such as GFAP, APP, and RTN4, in a mouse model of Alzheimer’s disease. The pronounced elevation of RTN4 in reactive astrocytes is indicative of its involvement in Alzheimer’s disease pathogenesis. Furthermore, we identified dysregulation of pathways related to endocytosis, highlighting the critical role of this process in disease progression. Our findings underscore the significant impact of post-transcriptional (N6-methyladenosine methylation) and post-translational (phosphorylation) protein modifications, which have been underrepresented in Alzheimer’s disease research. The significant contribution made by this study is the integrated, multi-level omics analysis that we carried out to investigate the complex biological changes that occur in Alzheimer’s disease. Our findings provide novel insights into Alzheimer’s disease pathogenesis and suggest potential therapeutic targets, such as RTN4.

Key words: amyloid-β, amyloid precursor protein/presenilin 1, astrocyte, endocytosis, glial fibrillary acidic protein, multi-omics, nerve regeneration, post-transcriptional modification, post-translational modification, RTN4