Glial profiling of human tauopathy brain demonstrates enrichment of astrocytic transcripts in tau-related frontotemporal degeneration

对人类tau蛋白病脑组织的胶质细胞谱分析表明,tau蛋白相关的额颞叶变性中星形胶质细胞转录本富集。

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Abstract

To understand how glia may be altered in frontotemporal degeneration with tau pathology (FTD-tau), we used a NanoString glial profiling panel to measure 770 transcripts related to glial biology in human control (n = 8), Alzheimer's disease (AD) (n = 8), and FTD-tau (n = 8) dorsolateral prefrontal cortex. Compared to control, 43 genes were upregulated and 86 genes were downregulated in the FTD-tau samples. Only 3 genes were upregulated and 2 were downregulated in AD. Pathway analysis revealed many astrocyte-, microglia-, and oligodendrocyte-related pathway scores increased in FTD-tau, while neuron-related pathway scores decreased. We compared these results to a previously published proteomic dataset containing many of the same samples and found that the targeted panel approach obtained measurements for genes whose proteins were not measured in the proteomics. Our results point to the utility of multiomic approaches and marked dysregulation of glia in FTD-tau.

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