The QSP model of TREM2 influences on inflammatory state of microglia in Alzheimer’s disease

Background Inflammation is one of the critical components in development neurodegenerative diseases. Microglia resident macrophages central nervous system. In AD brain, microglial cells are found close association with amyloid beta deposits. Histological examination brains as well cell culture studies have shown that interaction microglia fibrillar leads to their phenotypic activation. It increases activation and switches them from resting (M0) activating (M1 or M2) state release cytokines. The role progression unclear conflicting reports regarding detrimental protective contribution disease. QSP model was developed investigate influence TREM2 on inflammation microglia. Methods describes state, phagocytosis, TLR, P2×7 receptors, kinases, intracellular signaling pathways, apoptosis cells, response LPS, oligomeric cytokines (IL6, IL1b, TNFa), distribution brain into cerebrospinal fluid blood. Results correctly decreased increased cytokine pro-inflammation factors KO during LPS-induction. demonstrates that: 1) TREM decrease phagocytosis [1] 2) Ab increase inflammatory level [2] 3) Inhibitor PI3K (LY294002) decreases pathway (PI3K/FoxO/phagocytosis) [3]. Conclusions This can be used predict various conditions caused by diseases therapies targeting state. – PMID: 30548312 33065553 [3] 28842601