biostudies-literatureUnknown19Budny V<h4>Introduction</h4>The main genetic risk factor for Alzheimer's disease (AD) is the presence of the apolipoprotein E4 (<i>APOE4</i>) allele. While <i>APOE4</i> increases the risk of developing AD, the <i>APOE2</i> allele is protective and <i>APOE3</i> is risk-neutral. In the brain, APOE is primarily expressed by astrocytes and plays a key role in various processes including cholesterol and lipid transport, neuronal growth, synaptic plasticity, immune response and energy metabolism. Disruptions in brain energy metabolism are considered a major contributor to AD pathophysiology, raising a key question about how different APOE isoforms affect the energy metabolism of human astrocytes.<h4>Methods</h4>In this study, we generated astrocytes (iAstrocytes) from <i>APOE</i>-isogenic human inducedFrontiers in cellular neuroscience1603657https://www.ebi.ac.uk/biostudies/studies/S-EPMC12434100biostudies-literatureAPOE genotype-dependent differences in human astrocytic energy metabolism.PMC12434100Barros LFRust RKruger MBudny VZurcher KJRuminot Ide Leeuw SMRavotto LWeber RZBodenmann CWeber BTackenberg CfalseAPOE genotype-dependent differences in human astrocytic energy metabolism.<h4>Introduction</h4>The main genetic risk factor for Alzheimer's disease (AD) is the presence of the apolipoprotein E4 (<i>APOE4</i>) allele. While <i>APOE4</i> increases the risk of developing AD, the <i>APOE2</i> allele is protective and <i>APOE3</i> is risk-neutral. In the brain, APOE is primarily expressed by astrocytes and plays a key role in various processes including cholesterol and lipid transport, neuronal growth, synaptic plasticity, immune response and energy metabolism. Disruptions in brain energy metabolism are considered a major contributor to AD pathophysiology, raising a key question about how different APOE isoforms affect the energy metabolism of human astrocytes.<h4>Methods</h4>In this study, we generated astrocytes (iAstrocytes) from <i>APOE</i>-isogenic human induced2025-01-01T00:00:00Z20252026-06-02T05:25:51.03Z2026-04-14T03:13:59.808ZS-EPMC124341004095877610.3389/fncel.2025.1603657