HOW INTERPLAY BETWEEN INFLAMMASOME AND MIRNA IS ASSOCIATED WITH ALZHEIMER’S DISEASE

Abstract

Abstract The results of recent analyses showed that neuroinflammation—a key contributor to Alzheimer’s disease (AD)—is activated by protein complexes known as inflammasomes. The NLRP3 inflammasome protein complex is mostly studied in the central nervous system; it includes a protein encoded by the NLRP3 gene. Connections between inflammasomes, neuroinflammation, and AD may be regulated by small non-coding RNAs called microRNAs. These molecules have multiple ways to influence AD. For example, microRNA miR-107 may influence AD through regulation of the BACE1 gene expression involved in Aβ production. It remains unclear whether interplay of miR-107 and NRLP3 is associated with AD and whether mechanisms of such interplay differ among participants of LLFS and other studies. To address these questions, we evaluated associations with AD of interactions between genetic variants (SNPs) located in DNA encoding miR-107 and NLRP3 in participants of the LLFS and Framingham Heart Study using a logistic regression model with an interaction term. The facts that both datasets deal with data on related individuals and that many SNPs from either miR-107 or NLRP3 are in linkage disequilibrium were accounted for in these studies. The analysis of the Framingham data showed that the association with AD of the interaction between SNPs from miR-107 and the NLRP3 gene was statistically significant(p=6.71E-03; Bonferroni correction=7.14E-03). The association of the same interaction with AD was replicated in the analysis of LLFS data. These results indicate that in addition to regulating BACE1 expression and Aβ production, miR-107 may influence AD in interaction with the NLRP3 gene.