Role of B-1a B cells and T cell recruitment in the modulation and progression of Alzheimer’s disease pathology in an amyloid mouse model 4017
Year: 2025
Type: article
Abstract: Description Alzheimer’s Disease (AD) is a complex disease characterized by amyloid plaque pathology and inflammation. The role of B and T cells in the peripheral immune system has been increasingly investigated and these cells have been implicated in exacerbating AD pathology. Specifically, “pathogenic” aged B cells are increased with age and has been linked to the worsening of AD pathology. Here, we report that the B-1a B cells, which are primed for self-reactivity, show altered, pathogenic phenotypes coinciding with a decline in behavioral assays in the APPNL-G-F plaque-associated AD mouse model. This increased change occurs in a sex-specific manner and manifests prior to plaque saturation in the brain. Further, we find an infiltration of CD8 T cells into the brain both proximal to and independent of plaque location at a 12-month timepoint when plaque load is high in both sexes. These observations lead us to hypothesize that the alterations in the B-1a compartment earlier in disease ultimately results in a plaque environment that is defined by a recruitment of peripheral T cells and persistence of pro-inflammatory signaling cascade. To test this hypothesis, we utilize a combination of machine-learning analysis tools, behavioral assays, high-dimensional flow cytometry, and multiplexed immunohistochemistry. These findings provide insight into the complex and close interplay of self-reactive B cells and brain-infiltrating T cells in the severity of AD pathology. Funding Sources R01AG075978 Topic Categories Neuroimmunology (NEUR)
Source: The Journal of Immunology
Institutions: University of Rochester Medicine, University of Rochester
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4416448937
FWCI:
Cites:
Cited by:
Related to: