Fig. 7

CHI3L1’s role in the pathology of Alzheimer’s disease through modulation of neuroinflammation. As chronic inflammation progresses, astrocytes and microglia release proinflammatory mediators, including CHI3L1, cytokines, and chemokines. CHI3L1 regulates IL-6 levels, which in turn elevates IL-1β and TNF-α levels, disrupting the BBB and initiating neuroinflammation, ultimately leading to neuronal death. IL-6 activation stimulates astrocytes, with reactive astrocytes (marked by increased GFAP) promoting amyloid-beta (Aβ) aggregation and Tau phosphorylation. Through STAT3 activation, CHI3L1 promotes APP expression in neurons, further driving Aβ aggregation and cognitive decline. Additionally, CHI3L1 induces microglial activation by regulating IL-6, resulting in the production of IL-6, IL-1β, and TNF-α, which exacerbates neuroinflammation and disrupts neurotransmitter signaling. CHI3L1 also activates the MAPK and NF-κB pathways, contributing to Aβ accumulation and neuronal inflammation via RAGE activation in both astrocytes and neurons