Researchers link APOE4 to fat buildup in brain cells — Live Science

Researchers have identified a possible mechanism through which the APOE4 genetic variant, linked to an increased risk of late-onset Alzheimer’s disease, may contribute to the accumulation of lipid droplets in brain cells. Work by a team led by neuroscientist Li-Huei Tsai at the Massachusetts Institute of Technology points to disrupted Wnt signaling in oligodendrocytes — cells that form the myelin sheath of nerve fibers, Live Science reports .

Impaired lipid transport The APOE gene encodes proteins involved in transporting fats in the body and brain. According to the researchers, proteins associated with the APOE4 variant perform this function less effectively. Carrying APOE4 is linked to a threefold to 12-fold increase in the risk of late-onset Alzheimer’s disease.

Previously, the team found cholesterol accumulation in astrocytes — cells that support neuron function. In another study, APOE4 also caused cholesterol accumulation in oligodendrocytes. In laboratory mice, a drug that helped these cells get rid of excess cholesterol improved myelin formation and cognitive test results.

More current news is available on the UA.News Telegram channel Telegram . The role of Wnt signaling In the new study, published in the journal Cell Stem Cell, scientists grew APOE4 oligodendrocytes from stem cells and altered the activity of individual genes one at a time. The screening pointed to the Wnt signaling pathway, which enables communication between cells.

In particular, switching off the DKK1 gene, which restrains this signaling pathway, reduced the number of lipid droplets in the cells. Brain tissue samples from donors carrying APOE4 showed signs of reduced Wnt signaling. Further experiments suggested that APOE4 may reduce the supply of a protein needed to transmit Wnt signals: this protein was broken down by an enzyme whose level increased under the influence of APOE4.

In mice, blocking the enzyme restored Wnt signaling, reduced fat accumulation and improved myelin formation. The authors emphasize that the results have not yet been confirmed in humans.