Article
Intravital characterization of microglia in Alzheimer’s Disease
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Published: | August 25, 2015 |
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Alzheimer’s disease (AD) is a primary neurodegenerative disorder characterized by three major pathological hallmarks including neuronal loss, neurofibrillary tangles and accumulation of β-amyloid (Aβ) plaques. While microglia, the resident immune cells of the central nervous system (CNS), are believed to be ineffective at phagocytosing and clearing Aβ, there is evidence from transgenic AD mouse models suggesting that peripheral myeloid cells constitute a heterogeneous cell population with greater Aβ clearing capabilities.
To assess the ability of peripherally-derived myeloid cells in reducing Aβ plaque pathology, we developed a method to exchange the pool of resident microglia with peripherally-derived myeloid cells using CD11b-HSVTK mice, which allow for selective ablation of CD11b+ cells. Next, we established a multiphoton microscopy approach to intravitally monitor microglia depletion and subsequent rapid and large-scale infiltration of peripheral myeloid cells in order to characterize the different cell populations and their ability to clear Aβ in vivo.