APOE Variants: How Receptors and Lysosomes Influence Risk

A recent study published in Cell reveals that the risk of late-onset Alzheimer's disease associated with different APOE gene variants is linked to lysosomal dysfunction. Researchers found that the high-risk ApoE4 variant, unlike the protective ApoE2 and Christchurch variants, transports lipids into lysosomes, leading to the accumulation of lipofuscin, a toxic byproduct. This process is exacerbated by the strong binding of ApoE4 to low-density lipoprotein receptors, causing increased lipid uptake and oxidative stress in lysosomes. These findings offer new insights into the molecular mechanisms of Alzheimer's and potential therapeutic targets.