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12 Mar 2021
The E4 allele of the apolipoprotein E, a strong risk factor for many neurodegenerative diseases, most prominently late-onset Alzheimer’s disease, upsets the balance of lipids within cells. Exactly how ApoE4 does this remains unclear. In the March 3 Science Translational Medicine, researchers led by Li-Huei Tsai at MIT found that in human astrocytes and microglia, ApoE4 increased the amount of unsaturated lipids, which then accumulated in lipid droplets. Adding the phospholipid precursor choline to the cells restored their normal lipid metabolism, hinting at potential therapeutic approaches for ApoE4 carriers.
How exactly does ApoE4 lead to lipid imbalance in astrocytes?
Study offers an explanation for why the APOE4 gene enhances Alzheimer’s risk
March 4, 2021MIT
The gene variant disrupts lipid metabolism, but in cell experiments the effects were reversed by choline
One of the most significant genetic risk factors for developing Alzheimer’s disease is a gene called APOE4, which is carried by almost half of all Alzheimer’s patients. A new study from MIT shows that this gene has widespread effects on brain cells’ ability to metabolize lipids and respond to stress.
In studies of human brain cells and yeast cells, the researchers found that the APOE4 gene significantly disrupts brain cells’ ability to carry out their normal functions. They also showed that treating these cells with extra choline, a widely available supplement that is considered safe for human use, could reverse many of these effects.
A study by MIT researchers has provided new insights into the mechanisms by which a gene variant that is know to represent a risk factor for Alzheimer’s disease may impact on cellular lipid metabolism and stress response. Their studies in human brain cells and in yeast cells indicated how the APOE4 gene disrupts lipid homeostasis, and also showed that treating the cells with choline, a widely available dietary supplement, could reverse many of the effects of this disruption.
Headed by Li-Huei Tsai, PhD, director of MIT’s Picower Institute for Learning and Memory, the researchers hope that their findings may lead to clinical studies of choline specifically in people who carry the APOE4 gene, to see if the supplement could help to reduce the incidence of Alzheimer’s disease. Previous trials looking at choline’s effects on cognition have shown mixed results, but those trials were not targeted specifically to people with the APOE4 gene. The team is also now studying a mouse mode