Alzheimer’s disease (AD) is a neurodegenerative disease that causes progressive memory and cognitive impairment and is the most common type of dementia. Brain injury caused by neurodegeneration can induce reactive astrogliosis (RA), where astrocytes, the main glial cell type in the brain, change transcriptomically and morphologically and take on neuroinflammatory roles. One subtype of inflammatory RA found in AD patient brains releases neurotoxic compounds and has an elevated immune response.
We have previously shown that enhancers, a type of genetic regulatory element, regulate genes involved in both RA and AD. Here, we propose to first characterise the cellular transcriptome of reactive astrogliosis in astrocytes derived from the human brain using single cell RNA sequencing (scRNA-seq). We will then investigate the effects of silencing enhancers that regulate genes associated with astrogliosis and are associated with AD using CRISPR interference and determine transcriptional changes using scRNA-seq.