To what extent does PLCG2 expression have a positive impact on AD

Abstract

Late-onset Alzheimer’s disease (LOAD) is a prevalent form of AD that lacks a cure. Previous research has shown that PLCG2, associated with inflammatory response, influences AD by affecting amyloid plaque density. Inflammation plays a crucial role in AD progression, as Aβ activates microglia, triggering an inflammatory response with varied consequences for neuronal survival. This study aims to explore the impact of different PLCG2 expression levels on AD using 5xFAD mouse models. Four experiments were conducted to investigate the effect of PLCG2 expression on inflammation, amyloid plaque density, and cognitive function. The GAL4-UAS system and CRISPR-Cas9 system were employed for genetic modification, while immunofluorescence staining and the Morris water navigation task were used for analysis. Results indicate a positive correlation between PLCG2 expression and immune response, with the PLCG25x mice exhibiting the highest immune response. Additionally, higher PLCG2 expression levels were associated with slower growth in amyloid plaque density. The optimal PLCG2 expression level was found to be PLCG22x, which had a positive impact on AD conditions. This research provides valuable insights into the role of PLCG2 in AD pathogenesis and highlights the potential for PLCG2-directed therapeutics as a promising avenue for developing novel treatments for LOAD.