IMMUNE CELL INTERACTIONS IN AMYLOID-BETA PLAQUE PATHOLOGY

Abstract

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease in the Western world characterized by a progressive loss of cognitive functions leading to dementia. Besides others, AD is characterized by the formation of amyloid-beta plaques, which often co-localize with increased neuroinflammation, i.e. activation of brain resident glial cells, in particular microglia, as well as infiltrating peripheral immune cells. The function and interaction of peripheral immune cells with the brains microglia are so far not fully understood. By serendipity, we observed doublecortin (DCX; generally used as a marker for young immature neurons) positive cells located at sites of amyloid-beta plaques in various transgenic amyloid mouse models and in human AD specimen. Immunohistochemical fluorescence (IHC) staining was performed on human AD samples and free floating brain slices from transgenic amyloid mouse models. Sections were analysed by confocal laser scanning microscopy and APP-PS1 brain sections were immunogold stained for ultrastructure analysis by electron microscopy. Detailed IHC analysis in the APP-PS1 mouse model demonstrated that a fraction of the plaque-associated DCX+ cells showed co-expression of markers for microglia (Iba1+), while the Iba1 negative DCX+ cells were highly positive for the pan-leukocyte marker CD45. These DCX+/CD45+ cells express the classical T-cell marker CD3 and ultrastructure analysis revealed a close association of CD3+ cells with the brains resident microglia. It will be essential to uncover the functional interaction between these two cell types, as peripheral derived immune cells and their interaction with microglia might be a target for future therapeutic approaches in AD.