Regulation of beta-amyloid production in neurons by astrocyte-derived cholesterol

@article{Wang2020RegulationOB,
  title={Regulation of beta-amyloid production in neurons by astrocyte-derived cholesterol},
  author={Hui Wang and Joshua A. Kulas and Heather A. Ferris and Scott B. Hansen},
  journal={bioRxiv},
  year={2020}
}
Alzheimer’s Disease (AD) is characterized by the presence of β-Amyloid (Aβ) plaques, tau tangles, inflammation, and loss of cognitive function. Genetic variation in a cholesterol transport protein, apolipoprotein E (apoE), is the most common genetic marker for sporadic AD. In vitro evidence suggests apoE links to Aβ production through nanoscale lipid compartments (also called lipid rafts), but its regulation in vivo is unclear. Here we use super-resolution imaging in mouse brain to show apoE… Expand
6 Citations
Regulation of beta-amyloid production in neurons by astrocyte-derived cholesterol
TLDR
Superresolution imaging in the mouse brain is used to show that apoE utilizes astrocyte-derived cholesterol to specifically traffic neuronal amyloid precursor protein in and out of lipid clusters, where it interacts with β- and γ-secretases to generate Aβ-peptide. Expand
Beta-amyloid production in neurons is regulated by astrocyte-derived cholesterol
TLDR
It is shown that Aβ accumulation in neurons is tightly regulated by cholesterol production in astrocytes, which paves the way for future work that will establish whether the selective removal of Aβ by targeting this mechanism has therapeutic potential. Expand
Cholesterol and Alzheimer’s Disease; From Risk Genes to Pathological Effects
TLDR
The different systems that maintain brain cholesterol metabolism in the healthy brain are discussed, and how dysregulation of these processes can lead, or contribute to, Alzheimer’s disease. Expand
Hydroxychloroquine: mechanism of action inhibiting SARS-CoV2 entry.
TLDR
It is concluded HCQ is an anesthetic-like compound that disrupts GM1 lipid rafts similar to general anesthetics, which likely decreases viral clustering at both endocytic and putative PIP2 entry points. Expand
Astrocytic Factors Controlling Synaptogenesis: A Team Play
TLDR
Recent findings on novel mechanisms that regulate astrocyte-mediated synaptogenesis during development, and the control of synapse number in the critical period or upon synaptic plasticity are highlighted. Expand
The role of high cholesterol in age-related COVID19 lethality.
TLDR
Loading cells with cholesterol from blood serum using the cholesterol transport protein apolipoprotein E (apoE) enhances the entry of pseudotyped SARS-CoV-2 and the infectivity of the virion, and proposes a component of COVID19 severity based on tissue cholesterol level and the sensitivity of ACE2 and furin to cholesterol. Expand

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