Development and Assessment of a Prediction Model for Alzheimer's Disease Diagnosis Based on Thermoregulation-Related Genes

Abstract

Background: Alzheimer's disease (AD) is a prevalent neurodegenerative condition among the elderly population and the most common form of dementia, however, we lack potent interventions to arrest its inherent pathogenic vectors. Robust evidence indicates thermoregulatory perturbations during and before the onset of symptoms. Therefore, temperature-regulated biomarkers may offer clues to therapeutic targets during the presymptomatic stage. Objective: The purpose of this study is to develop and assess a thermoregulation-related gene prediction model for Alzheimer's Disease diagnosis. Method: This study aims to utilize microarray bioinformatic analysis to identify the potential biomarkers of AD by analyzing four microarray datasets (GSE48350, GSE5281, GSE122063, and GSE181279) of AD patients. Furthermore, thermoregulation-associated hub genes were identified, and the expression patterns in the brain were explored. In addition, we explored the infiltration of immune cells with thermoregulation-related hub genes. Diagnostic marker validation was then performed at the single-cell level. Finally, the prediction of targeted drugs was performed based on the hub genes. Results: Through the analysis of four datasets pertaining to AD, a total of five genes associated with temperature regulation were identified. Notably, CCK, CXCR4, SLC27A4, and SLC17A6 emerged as diagnostic markers indicative of AD-related brain injury. Furthermore, in the examination of peripheral blood samples from AD patients, SLC27A4 and CXCR4 were identified as pivotal diagnostic indicators. Regrettably, animal experimentation was not pursued to validate the data; rather, an assessment of temperature regulation-related genes was conducted. Future investigations will be undertaken to establish the correlation between these genes and AD pathology. Conclusion: Overall, CCK, CXCR4, SLC27A4, and SLC17A6 can be considered pivotal biomarkers for diagnosing the pathogenesis and molecular functions of AD.