Figure 3

Cross-talk of membrane lipids and Alzheimer-associated proteins. Alterations in membrane lipid composition affect secretase activities, thereby modulating APP processing and generation of Aβ. Alternatively, membrane lipids can directly interact with Aβ and modulate its aggregation. In addition, membrane lipids impair the metabolism of tau. Thus, both neuropathological hallmarks of AD could be triggered by age-dependent changes in lipid metabolism. Conversely, membrane lipid composition is affected by APP and its derivatives Aβ and CTFβ, which were shown to modulate lipid metabolic enzymes and directly bind membrane lipids including cholesterol and gangliosides. Tau also affects membrane lipid composition, likely via regulation of vesicular transport. ApoE as a major lipoprotein in the brain could also affect lipid composition, but also Aβ clearance and aggregation. Solid arrows indicate a direct interaction of the respective components whereas dotted arrows indicate potential modulations by yet undefined mechanisms. See text for further details.