Heightened effector immune cell infiltration of the hippocampus concurrently with brain ventricular volume expansion in aged APP/PS1 mice

Alzheimer's disease (AD) is the most common form of dementia for which the role of neuroinflammation is becoming more realized. Recent studies have shown that immune cells infiltrate the hippocampus and the cortex of AD patients as well as mouse models of the disease. In this study, we employed T2-weighted magnetic resonance imaging (MRI) to view changes in ventricular volume in addition to spectral flow cytometric assessment of the hippocampus infiltrating immune profile in the aged APP/PS1 mice. Aged APP/PS1 mice present with increased size of lateral, dorsal, and ventral ventricles plus increased numbers of hippocampus infiltrating effector immune cell subsets, including CD8 T cells expressing IFNγ, granzyme B, and perforin along with other cell types such as γδ T cells, neutrophils, and NK cells. The concurrent increase in effector cell types with ventricular enlargement expands the putative mechanism of brain atrophy in the APP/PS1 mouse model to include cytolytic functions of these aforementioned immune cell subsets.