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

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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.