Elevated plasma triglyceride levels precede amyloid deposition in Alzheimer’s disease mouse models with abundant Aβ in plasma

Dietary or pharmacological manipulation of plasma lipids markedly influences amyloid deposition in animal models of Alzheimer’s Disease (AD). However, it is not known whether baseline plasma lipids in AD models differ from wild-type littermates throughout the natural history of disease. To address this question, we measured plasma total cholesterol and triglyceride levels over time in three transgenic AD mouse models in the absence of dietary or pharmacological treatments. Total cholesterol levels were not significantly different between transgenic and wild-type mice during the development of AD neuropathology in all models tested. In contrast, elevated very-low-density lipoprotein (VLDL) triglyceride levels preceded amyloid deposition in two AD models with abundant plasma Aβ. Elevated triglycerides were not accompanied by increased inflammatory markers nor decreased lipase activity, but were associated with a significant 30% increase in VLDL-triglyceride secretion rate. Our results suggest that the presence of Aβ in plasma may affect peripheral lipid metabolism early in AD pathogenesis.