According to the widely-held amyloid hypothesis of AD, Ab initiates an array of molecular. However, mechanistic molecular processes that link Ab and neurodegeneration remain to be firmly established. Chronic neuroinflammation associated with persistent glial activation is a major disease process evoked by Ab and intimately associated with the progress of AD pathologies. Previous studies suggest that neuroinflammation contributes to the development of neurodegenerative hallmarks in AD brains, including Ab plaques and tau tangles. AD therapeutic approaches that target neuroinflammation are under development. AD neuroinflammation is likely triggered by Ab-mediated activation of microglia and astrocytes. It was reported that Ab induces the expression of cytokines in cultured astrocytes and microglia. Mounting evidence suggests that Ab may activate glial cells via specific sensor receptors such as toll-like receptors, receptors for advanced glycoxidation end-products and NOD-like receptors. Despite the significant understandings on the induction of AD neuroinflammation, the downstream molecular processes that are elicited by Ab and regulate the inflammation remain poorly understood. Wnts are secreted signaling proteins that play important roles in neural development and plasticity. Multiple lines of evidence indicate a critical role of Wnt signaling in AD. bcatenin, a key downstream effector protein in the GDC-0199 Bcl-2 inhibitor canonical Wnt signaling pathway, interacts with and is regulated by presenilin. Glycogen synthase kinase -3, a central serine/ threnine kinase in the canonical Wnt signaling pathway, plays a critical role in the regulation of Ab production and aggregation and in tau phosphorylation. Genetic studies revealed that LRP6 polymorphisms are causally linked to AD. In AD brains, canonical Wnt signaling is impaired, and DKK1, an antagonist of Wnt signaling, is upregulated. Importantly, Ab was reported to inhibit Wnt signaling by directly binding to the Frizzled receptors. The impairment of canonical Wnt signaling is likely etiologically significant, because forced up-regulation of the canonical Wnt signaling pathway has rescuing effects on the development of AD-related phenotypes in both neuron cultures and animal models. In contrast to the canonical pathway, the involvement of non-canonical Wnt signaling pathways in the regulation of AD pathogenesis is less clear. A recent study indicates that Wnt5a-activated non-canonical Wnt signaling antagonizes Ab synaptotoxicity.