APOE4/4 is linked to damaging lipid droplets in Alzheimer’s disease microglia

Haney, Michael S.; Pálovics, Róbert; Munson, Christy; Long, Chris M.; Johansson, Patrik K.; Yip, Oscar; Dong, Wentao; Rawat, Eshaan S.; West, Elizabeth; Schlachetzki, Johannes C. M.; Tsai, Andy P.; Guldner, Ian H.; Lamichhane, Bhawika S.; Smith, Amanda; Schaum, Nicholas; Calcuttawala, Kruti; Shin, Andrew; Wang, Yung-Hua; Wang, Chengzhong; Koutsodendris, Nicole; Serrano, Geidy E.; Beach, Thomas G.; Reiman, Eric M.; Glass, Christopher K.; Abu-Remaileh, Monther; Enejder, Annika; Huang, Yadong; Wyss‐Coray, Tony

doi:10.1038/s41586-024-07185-7

articleNatureMar 13, 2024HYBRID OA

APOE4/4 is linked to damaging lipid droplets in Alzheimer’s disease microglia

MSMichael S. Haney RPRóbert Pálovics CMChristy Munson CMChris M. Long PKPatrik K. Johansson

Neurosciences Institute · Stanford University · +7 more institutions

PubMed

Indexed incrossrefpubmed

Abstract

. However, the relationship between lipid metabolism in glia and Alzheimer's disease pathology remains poorly understood. Through single-nucleus RNA sequencing of brain tissue in Alzheimer's disease, we have identified a microglial state defined by the expression of the lipid droplet-associated enzyme ACSL1 with ACSL1-positive microglia being most abundant in patients with Alzheimer's disease having the APOE4/4 genotype. In human induced pluripotent stem cell-derived microglia, fibrillar Aβ induces ACSL1 expression, triglyceride synthesis and lipid droplet accumulation in an APOE-dependent manner. Additionally, conditioned media from lipid droplet-containing microglia lead to Tau phosphorylation and…

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Topics & keywords

Topics

Keywords

Microglia
Apolipoprotein E
Lipid metabolism
Neurotoxicity
Lipid droplet
Neurodegeneration
Biology
Alzheimer's disease

UN Sustainable Development Goals

Good health and well-being

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