NIH Research Festival
Alzheimer‚Äôs Disease (AD) is neurodegenerative disease linked to accumulation of AŒ≤ plaques, neurofibrillary tangles, and chronic neuroinflammation. Although the role of the adaptive immunity in AD remains poorly understood, recent findings indicate that CD8+ T cells increase in the AD brain. Our aim was to characterize CD8+ T-cells and to investigate if they are required in AD progression. We immunized female 5xFAD mice at pre- (2-3 months) and post-onset of AD (7-8 months) with an AŒ≤-CoreS RNA vaccine encoding AÔÅ¢1-11 on the surface of HBsAg particles. The CD8+ T cells were quantified from the brain of these mice and unvaccinated 5xFAD mice using immunofluorescence (IF) staining (n=4-7). We further characterized the activation state of brain CD8+ T cells from saline perfused 5xFAD mice using flow cytometry (n = 8-11). Similarly, stained humans tissued with AD (79-90 years old) were quantified for CD8+ T-cells. Our results reveal that compared to WT, AD significantly increases brain CD8+ T cells exhibiting cytotoxic but exhausted phenotype. These affects were significantly increased in vaccinated mice, linking the increase of brain CD8+ T cells to the exacerbation of AD. The brain CD8+ T cells positively correlated with cognitive decline and AŒ≤ plaque accumulation with their activation induced in the periphery. To do this, they likely target microglia, as in both mice and humans with AD we detected significantly more brain CD8+ T cells tightly attached to activated microglia than in non-AD groups. Overall, our results indicate that brain CD8+ T cells play pathogenic role in AD.
Scientific Focus Area: Immunology
This page was last updated on Monday, September 25, 2023