Your new experience awaits. Try the new design now and help us make it even better

ORIGINAL RESEARCH article

Front. Neurosci.

Sec. Neurodegeneration

Volume 19 - 2025 | doi: 10.3389/fnins.2025.1663276

This article is part of the Research TopicEarly Dementia Detection: Memory, Cortical Function, and Biomarkers in the Classification of High-Risk Pre-Dementia Individuals in the Healthy Aging PeopleView all 7 articles

Plasma FGF2 and YAP1 as Novel Biomarkers for MCI in the Elderly: Analysis via Bioinformatics & Clinical Study

Provisionally accepted
Yejing  ZhaoYejing ZhaoXiang  WangXiang WangZhang  JieZhang JieYanyan  ZhaoYanyan ZhaoYi  LiYi LiJi  ShenJi ShenYing  YuanYing YuanJing  LiJing Li*
  • Beijing Hospital, Beijing, China

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

The contemporary consensus firmly emphasizes the urgent need to reorient research efforts towards the early detection of preclinical Alzheimer's disease (AD) or mild cognitive impairment (MCI). However, there is still a notable absence of novel biomarkers that are both efficient, minimally invasive, and cost-effective in real-world clinical settings. To address this gap, datasets GSE29378 and GSE12685 were selected to screen differentially expressed genes (DEGs), and hub genes were identified by different algorithms. A total of 350 DEGs were identified in bioinformatics data mining. Functional enrichment analysis showed that fibroblast growth factor 2(FGF2) and yes-associated protein 1(YAP1) protein levels were highly expressed in AD samples, indicating their potential regulatory roles in AD. Between October and November 2024, a total of 146 elderly individuals diagnosed with MCI and 54 healthy elderly subjects were successfully recruited. Enzyme linked immunosorbent assay (ELISA) was used to detect plasma hub gene protein concentration. The results showed that the expression levels of plasma FGF2 and YAP1 proteins in the MCI group were significantly higher compared to the control group. Logistic regression analysis indicated that high plasma FGF2 and YAP1 expression levels were independently associated with MCI in the elderly. The Area under the curve (AUC) of FGF2 model and YAP1 model were 0.907 and 0.972, respectively. Therefore, the high expression of plasma FGF2 and YAP1 proteins may be independent predictive risk factors for MCI in the elderly. Our findings may provide targets for the development of early minimally invasive, efficient, and convenient screening tools, and even for the treatment of AD in the future.

Keywords: Alzheimer's disease, Mild Cognitive Impairment, FGF2, Yap1, biomarkers

Received: 10 Jul 2025; Accepted: 13 Aug 2025.

Copyright: © 2025 Zhao, Wang, Jie, Zhao, Li, Shen, Yuan and Li. 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: Jing Li, Beijing Hospital, Beijing, China

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.