Fig. 3

Mechanisms of lipid involvement in Aβ metabolism. Summary of the regulatory roles of lipids in multiple stages of Aβ metabolism. (1) Lipid component in cellular organelles such as endoplasmic reticulum (ER), Golgi apparatus, and endosome can regulate the intracellular trafficking and enzymatic processing of APP. Elevated sulfatides, PUFAs and PI(3)P (green font) are considered to lower Aβ generation, while induction of cholesterol and ceramides (red font) promotes Aβ production. (2) Lipids can also impact Aβ levels by transcriptional regulation of APP secretases (e.g., 27-hydorxycholetserol promotes β- secretase expression). (3) Interaction of cholesterol, gangliosides, and phospholipids with Aβ induces Aβ fibrillation. (4) Sulfatides facilitate ApoE-mediated Aβ uptake. (5) Exosome-mediated Aβ secretion can impact Aβ load by enzymatic degradation or facilitating nucleation via Aβ-phospholipid interaction