The peripheral immune system in Alzheimer's disease (AD) has not been thoroughly studied with modern sequencing methods. To investigate epigenetic and transcriptional alterations to the AD peripheral immune system, we used single-cell sequencing strategies, including assay for transposase-accessible chromatin and RNA sequencing. We reveal a striking amount of open chromatin in peripheral immune cells in AD. In CD8 T cells, we uncover a cis-regulatory DNA element co-accessible with the CXC motif chemokine receptor 3 gene promoter. In monocytes, we identify a novel AD-specific RELA transcription factor binding site adjacent to an open chromatin region in the nuclear factor kappa B subunit 2 gene. We also demonstrate apolipoprotein E genotype-dependent epigenetic changes in monocytes. Surprisingly, we also identify differentially accessible chromatin regions in genes associated with sporadic AD risk. Our findings provide novel insights into the complex relationship between epigenetics and genetic risk factors in AD peripheral immunity.
Keyphrases
- transcription factor
- genome wide
- single cell
- gene expression
- dna methylation
- nuclear factor
- genome wide identification
- chemotherapy induced
- rna seq
- dna damage
- copy number
- high throughput
- dna binding
- risk factors
- toll like receptor
- dendritic cells
- immune response
- oxidative stress
- cognitive decline
- late onset
- early onset
- inflammatory response
- minimally invasive
- nucleic acid
- circulating tumor cells
- mild cognitive impairment
- protein kinase