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APOE4-carrying human astrocytes oversupply cholesterol to promote neuronal lipid raft expansion and Aβ generation

Title
APOE4-carrying human astrocytes oversupply cholesterol to promote neuronal lipid raft expansion and Aβ generation
Author(s)
Lee, Se-InJeong, WoojinLim, HeejinCho, SukheeLee, HyeinJang, YongheeCho, JoonhoBae, SimsungLin, Yuan-TaTsai, Li-HueiMoon, Dae WonSeo, Jinsoo
DGIST Authors
Lee, Se-InJeong, WoojinLim, HeejinCho, SukheeLee, HyeinJang, YongheeCho, JoonhoBae, SimsungLin, Yuan-TaTsai, Li-HueiMoon, Dae WonSeo, Jinsoo
Issued Date
2021-09
Type
Article
Author Keywords
Alzheimer&aposs diseaseapolipoprotein Echolesterolhuman induced pluripotent stem cellslipid rafts
Keywords
APPDISEASEDYSREGULATIONMECHANISMS
ISSN
2213-6711
Abstract
The epsilon 4 allele of APOE-encoding apolipoprotein (ApoE) is one of the strongest genetic risk factors for Alzheimer's disease (AD). One of the overarching questions is whether and how this astrocyte-enriched risk factor initiates AD-associated pathology in neurons such as amyloid-B (AB) accumulation. Here, we generate neurons and astrocytes from isogenic human induced pluripotent stem cells (hiPSCs) carrying either APOE epsilon 3 or APOE epsilon 4 allele and investigate the effect of astrocytic ApoE4 on neuronal AB production. Secretory factors in conditioned media from ApoE4 astrocytes significantly increased amyloid precursor protein (APP) levels and AB secretion in neurons. We further found that increased cholesterol secretion from ApoE4 astrocytes was necessary and sufficient to induce the formation of lipid rafts that potentially provide a physical platform for APP localization and facilitate its processing. Our study reveals the contribution of ApoE4 astrocytes to amyloidosis in neurons by expanding lipid rafts and facilitating AB production through an oversupply of cholesterol.
URI
http://hdl.handle.net/20.500.11750/15598
DOI
10.1016/j.stemcr.2021.07.017
Publisher
Cell Press
Related Researcher
  • 문대원 Moon, Dae Won 뉴바이올로지전공
  • Research Interests Coherent Raman Scattering; Surface Plasmon Resonance Imaging Ellipsometry; Imaging Mass Spectrometry; Time-of-flight Medium Energy Ion Scattering
Files in This Item:
Lipid rafts.pdf

Lipid rafts.pdf

기타 데이터 / 2.83 MB / Adobe PDF download
Appears in Collections:
Department of New Biology ETC 1. Journal Articles
Department of New Biology NanoBio Imaging Laboratory 1. Journal Articles
Department of Brain Sciences Laboratory of Aging Brain 1. Journal Articles

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