Characterization of the transcriptome and TCR of brain and cerebrospinal fluid infiltrated CD8 +T cells in an Alzheimer’s disease mouse model

Abstract

Abstract Alzheimer’s disease (AD) is a common form of dementia characterized by the accumulation of protein aggregates in the brain of older adults. It has been observed that CD8 +T cells, particularly CD8 +TEMRA cells, infiltrate the brain and cerebrospinal fluid (CSF) of AD patients. However, the precise role of these cells in the development and progression of AD is not well understood. In this study, we used single-cell RNA sequencing (scRNAseq) and single-cell T cell receptor sequencing (scTCRseq) to examine the CD8 +T cells in the brain and CSF of a mouse model of AD (5xFAD) and its wild-type (WT) littermate controls. The AD mice (age 40–70 weeks) used in our experiments have developed memory deficits. Our analysis revealed a significant increase in the number of CD8 +T cells in the brain and CSF of AD mice compared to WT controls (n=4, p<0.05). Furthermore, these cells displayed a distinct transcriptome profile characterized by increased expression of inflammatory pathways, compared to WT mice. Through TCR sequence analysis, we also observed significant clonal expansion of CD8 +T cells in AD mice compared to WT mice. These findings provide a starting point for further investigation into the role of infiltrating CD8 +T cells in the pathogenesis of AD in this mouse model.