Single Cell Transciptomics of the Opioid Use Disorder and HIV Syndemic in the Human Brain

使中枢神经系统血管化的血管具有独特的性质，称为 血脑屏障（BBB），它对分子和细胞施加严格的调节 （特别是免疫细胞）在血液和大脑之间移动。血脑屏障破坏可能 增加免疫细胞向脑实质的浸润，促进胶质细胞活化， 增加炎症和神经毒性。有趣的是，血脑屏障通透性增加， 与阿尔茨海默病的发展有关细胞间差异基因表达 类型和个体之间可能有助于选择性脆弱性或弹性。这 一项提案将使用单核RNA测序来阐明细胞类型选择性转录组 在AD和对照病例的软脑膜和相关免疫细胞中。这项工作将导致 我们对细胞类型特异性基因调控的认识有了根本性的进展， AD中神经血管和相关免疫细胞类型的病理生理学。

Blood vessels that vascularize the central nervous system possess unique properties, termed the blood-brain barrier (BBB), which imposes a tight regulation of molecules and cells (particularly immune cells) that move between the blood and the brain. Disrupted BBB may increase immune cell infiltrating into the brain parenchyma and promote glial activation, increased inflammation and neurotoxicity. Interestingly, increased permeability of BBB has been implicated in the progression of Alzheimer's disease. Differential gene expression among cell types, and among individuals likely contributes to selective vulnerability or resilience. This proposal will use single nucleus RNA sequencing to elucidate cell type selective transcriptomes in leptomeninges and associate immune cells from AD and control cases. This work will lead to fundamental advances in our knowledge of cell type specific genes regulating the pathophysiology of neurovasculature and associate immune cell types in AD.