Changes in Expression of Key Genes in Alzheimer's Disease: A Specific Brain Tissue Change

• Published in: The journals of gerontology. Series A, Biological sciences and medical sciences Biological sciences and medical sciences, 2024-05, Vol.79 (5)
• Main Authors: Rasmussen, Lucas Trevizani, de Labio, Roger Willian, Dos Santos, Mônica Pezenatto, Fredi, Bruno Mari, Chagas, Eduardo Federighi Baisi, Chen, Elizabeth Suchi, Turecki, Gustavo, de Arruda Cardoso Smith, Marília, Payão, Spencer Luiz Marques
• Format: Article
• Language: English
• ISSN: 1079-5006; 1758-535X
• DOI: 10.1093/gerona/glae023

Alzheimer's disease (AD) is an irreversible and neurodegenerative disorder. Its etiology is not clear, but the involvement of genetic components plays a central role in the onset of the disease. In the present study, the expression of ten genes (APP, PS1 and PS2, APOE, APBA2, LRP1, GRIN2B, INSR, GJB1, and IDE) involved in the main pathways related to Alzheimer's disease were analyzed in auditory cortices and cerebellum from 29 AD patients and 29 healthy older adult. Raw analysis revealed tissue-specific changes in genes LRP1, INSR and APP. A correlation analysis showed a significant effect also tissue-specific of AD in APP, GRIN2B, INSR and LRP1. Furthermore, E4 allele of the APOE gene revealed a significant correlation with change expression tissue-specific in ABPA2, APP, GRIN2B, LRP1 and INSR genes. To assess the existence of a correction between changes in target gene expression and a probability of AD in each tissue (auditory cortices and cerebellum) an analysis of the effect of expressions was realized and showed that the reduction in the expression of the APP in auditory cortex and GRIN2B cerebellum in had a significant effect in increasing the probability of AD, in the same logic, our result also suggesting that increased expression of the LRP1 and INSR genes had a significant effect on increasing the probability of AD. Our results showed tissue-specific gene expression alterations associated with Alzheimer's disease and certainly open new perspectives to characterize factors involved in gene regulation and to obtain possible biomarkers for AD.