Fig. 4

Mechanisms of lipid involvement in tau pathology. Schematic summary of the roles of lipids in regulating tau phosphorylation, aggregation, and secretion. Disrupted lipid homeostasis or associated inflammation can trigger kinase activation, which often leads to hyperphosphorylation of tau. Tau monomers interact with negatively charged phospholipids in the membrane which facilitate the formation of tau fibrils and oligos. The direct secretion of tau through membrane is mediated through its interaction with membrane lipids including cholesterol, sphingolipids, and PI(4,5)P2, and further facilitated by HSPGs