Transcriptional response of murine microglia in Alzheimer's disease and inflammation

Background Alzheimer's disease (AD) is a neurodegenerative disorder and is the most common cause of late-onset dementia. Microglia, the primary innate immune cells of the central nervous system (CNS), have a complex role in AD neuropathology. In the initial stages of AD, microglia play a role in limiting pathology by removing amyloid-beta (A beta) by phagocytosis. In contrast, microglia also release pro-inflammatory cytokines and chemokines to promote neuroinflammation and exacerbate AD neuropathology. Therefore, investigating microglial gene networks could identify new targets for therapeutic strategies for AD. Results We identified 465 differentially expressed genes (DEG) in 5XFAD versus wild-type mice by microarray, 354 DEG in lipopolysaccharide (LPS)-stimulated N9 microglia versus unstimulated control cells using RNA-sequencing (RNA-seq), with 32 DEG common between both datasets. Analyses of the 32 common DEG uncovered numerous molecular functions and pathways involved in A beta phagocytosis and neuroinflammation associated with AD. Furthermore, multiplex ELISA confirmed the induction of several cytokines and chemokines in LPS-stimulated microglia. Conclusions In summary, AD triggered multiple signaling pathways that regulate numerous genes in microglia, contributing to A beta phagocytosis and neuroinflammation. Overall, these data identified several regulatory factors and biomarkers in microglia that could be useful in further understanding AD neuropathology.

Automated summary

The study revealed that AD activates multiple signaling pathways that regulate numerous genes in microglia, contributing to Aβ phagocytosis and neuroinflammation. These findings identified several regulatory factors and biomarkers in microglia, which could be beneficial for further comprehension of AD neuropathology.