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Report Vascular ApoE4 Impairs Behavior by Modulating Gliovascular Function

机译:通过调节岩手功能报告血管ApoE4损害行为

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摘要

The epsilon 4 allele of the apolipoprotein E gene (APOE4) is a strong genetic risk factor for Alzheimer's disease (AD) and multiple vascular conditions. ApoE is abundantly expressed in multiple brain cell types, including astrocytes, microglia, and vascular mural cells (VMCs). Here, we show that VMC-specific expression of apoE4 in mice impairs behavior and cerebrovascular function. Expression of either apoE3 or apoE4 in VMCs was sufficient to rescue the hypercholesterolemia and atherosclerosis phenotypes seen in Apoe knockout mice. Intriguingly, vascular expression of apoE4, but not apoE3, reduced arteriole blood flow, impaired spatial learning, and increased anxiety-like phenotypes. Single-cell RNA sequencing of vascular and glial cells revealed that apoE4 in VMCs was associated with astrocyte activation, while apoE3 was linked to angiogenic signature in pericytes. Together, our data support cell-autonomous effects of vascular apoE on brain homeostasis in an isoform-dependent manner, suggesting a critical contribution of vascular apoE to AD pathogenesis.
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  • 来源
    《Neuron》 |2021年第3期|共17页
  • 作者单位

    Mayo Clin Dept Neurosci Jacksonville FL 32224 USA;

    Mayo Clin Dept Neurosci Jacksonville FL 32224 USA;

    Mayo Clin Dept Neurosci Jacksonville FL 32224 USA;

    Mayo Clin Dept Neurosci Jacksonville FL 32224 USA;

    Mayo Clin Dept Neurosci Jacksonville FL 32224 USA;

    Mayo Clin Dept Neurosci Jacksonville FL 32224 USA;

    Mayo Clin Dept Neurosci Jacksonville FL 32224 USA;

    Mayo Clin Dept Neurosci Jacksonville FL 32224 USA;

    Mayo Clin Dept Neurosci Jacksonville FL 32224 USA;

    Mayo Clin Dept Hlth Sci Res Jacksonville FL 32224 USA;

    Mayo Clin Div Biomed Stat &

    Informat Rochester MN 55902 USA;

    Mayo Clin Dept Neurosci Jacksonville FL 32224 USA;

    Mayo Clin Dept Hlth Sci Res Jacksonville FL 32224 USA;

    Mayo Clin Neurosci Grad Program Jacksonville FL 32224 USA;

    Mayo Clin Dept Hlth Sci Res Jacksonville FL 32224 USA;

    Univ Texas MD Anderson Canc Ctr Dept Neurosurg Houston TX 77030 USA;

    Mayo Clin Dept Neurosci Jacksonville FL 32224 USA;

    Mayo Clin Dept Neurosci Jacksonville FL 32224 USA;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 神经病学;
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