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AAIC 2023 | The effect of APOE on the lipidome of individual brain cell types

Femke M Feringa, PhD, Vrije Universiteit Amsterdam, Amsterdam, Netherlands, discusses the effect of APOE risk variants on lipid metabolism and transport. APOE polymorphic alleles are known to be the major risk determinants for Alzheimer’s Disease (AD) and have been shown to affect the lipidome of human brain cell types. In this study, lipidomic analysis was undertaken on induced pluripotent stem cell (iPSC)-derived neurons, astrocytes, and microglia. The group also co-cultured these cell types to determine the effect of APOE variants on lipid transport between neurons and glia. The group discovered that APOE variants affect the lipidome of all tested brain cell types in cell type specific manner. In both microglia and astrocytes, the APOE4 allele increased lipid storage, however in neurons it reduced lipid storage. The group also discovered that the APOE allele present contributes to the transportation of lipids from neurons to glia and the resultant secretion of inflammatory IL-6. This was seen to be stronger in cells with the APOE3 variant compared to those with APOE4. This interview took place at the Alzheimer’s Association International Conference® (AAIC) 2023 in Amsterdam, Netherlands.

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