T Cell Exhaustion and the Role of Infections in Alzheimer ' s Disease

In this study we examined immune system alterations early in the progression to Alzheimer's disease (AD). We observed multiple changes across the peripheral innate and adaptive immune systems associated with amyloid and cognitive status within our aging cohort. In the innate immune system, we observed increased plasmacytoid and myeloid dendritic cells in amyloid positive participants, but these changes were particularly pronounced in those with mild cognitive impairment. We also observed a decrease in total natural killer cells with amyloid positivity. When the adaptive immune system was examined, we observed increases in total T cells and B cells in amyloid positive participants. To further understand alterations in the T cell pool we used flow cytometry to interrogate T cell differentiation and function. We observed an increase in differentiated CD4+ and CD8+ T cell phenotypes in amyloid positive participants with mild cognitive impairment. Surprisingly, we observed an increase in functional CD4+ and CD8+ T cells in amyloid positive cognitively normal participants, while those from amyloid positive mild cognitive impairment subjects had a dramatic increase in exhausted T cells. Importantly when T cell function was compared to cognitive status as determined by mini-mental state examination (MMSE), patients with the lowest score had the highest number of exhausted cells. Understanding how inflammation and the immune response control the development of AD is crit...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs