Biomarkers in Alzheimer’s disease progression: a longitudinal cohort study of NPTX2, GRIA1, and GRIA4

Jin, Kunpei1,#; Lv, Zhengyang1,#; Pang, Xinping2; Zhu, Chengjiang1; Liu, Ronghong1; Wei, Yanyu3,4,*; Pang, Chaoyang1,*

1College of Computer Science, Sichuan Normal University, Chengdu, Sichuan Province, China

2West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, Sichuan Province, China

3School of Information and Software Engineering, University of Electronic Science and Technology of China, Chengdu, Sichuan Province, China

4National Key Laboratory of Science and Technology on Vacuum Electronics, School of Electronic Science and Engineering, University of Electronic Science and Technology of China, Chengdu, Sichuan Province, China

*Correspondence to: Yanyu Wei, PhD, yywei@uestc.edu.cn; Chaoyang Pang, PhD, cypang@sicnu.edu.cn.

#Both authors contributed equally to this paper.

Abstract

Early diagnosis and intervention are vital for slowing Alzheimer’s disease progression and improving the quality of life in older people. Mild cognitive impairment, an early stage of Alzheimer’s disease, offers a key opportunity for research and intervention. However, current diagnostic methods are typically applied after significant symptoms appear, limiting the effectiveness of early intervention. The data of middle-aged and older individuals collected from the publicly available NCBI datasets GSE5281 and GSE1297 were included in this longitudinal cohort study. The cognitive status changes in participants over time were assessed using standard cognitive assessment tools, such as the Mini-Mental State Examination, along with mild cognitive impairment-specific tools. There was a significant negative correlation between Mini-Mental State Examination scores and the expression levels of neuronal pentraxin 2, glutamate receptor ionotropic AMPA 1 and 4. These results suggest that higher expression levels of these genes are associated with more severe cognitive impairment, highlighting their potential as biomarkers for the early detection of mild cognitive impairment. This study provides new insights into the molecular mechanisms underlying cognitive decline in older people and suggests directions for future research.

阿尔茨海默病进展中的生物标志物：一项纵向队列研究

摘要

早期诊断和干预对于减缓阿尔茨海默病进展和改善患者生活质量至关重要。然而，目前的诊断方法通常是在出现明显症状后才使用，从而限制了早期干预的效果。这项纵向队列研究纳入来源于NCBI 网站公开数据集 GSE5281 和 GSE1297 中无明显认知功能障碍的中老年人为研究对象。使用标准认知评估工具，如简易精神状态检查表和轻度认知障碍专用工具评估研究对象认知状态随时间的变化。结果显示，简易精神状态检查表评分与神经细胞穿透素2、谷氨酸受体离子型 AMPA 1 和 4 的表达水平呈显著负相关。这些结果表明，神经细胞穿透素2、谷氨酸受体离子型 AMPA 1 和 4基因的表达水平越高，认知功能损害越严重，这凸显了这些基因作为检测认知功能损害程度的生物标志物潜力。