A key role for glia in the brain is the phagocytosis of misfolded Aβ and glial phagocytic dysfunction is a major contributing factor to AD. To differentiate between the phagocytic and non-phagocytic glia in vitro and in vivo, we developed a pH-conjugated fluorophore of Aβ (AβpH) that only exhibits bright green fluorescence upon its phagocytic uptake into the acidic lysosomes. This work showed that microglia phagocytose AβpH much more than astrocytes and that AβpH can be used to monitor, for the first time, Aβ-specific phagocytosis in live animals in real-time.
Additionally, we also developed a rapid, robust, and refined method to produce large quantities of recombinant human Aβ 1-42 using molecular biology and analytical chemistry techniques. Here, we showed that the recombinant Aβ exhibits similar aggregative properties to the synthetic Aβ and can be used in downstream biological experiments. Finally, we developed new pH-activable probes to visualize intracellular organelles in glia. Together, these tools have allowed us to answer questions related to glial functions in the context of neurodegeneration.
Additionally, we also developed a rapid, robust, and refined method to produce large quantities of recombinant human Aβ 1-42 using molecular biology and analytical chemistry techniques. Here, we showed that the recombinant Aβ exhibits similar aggregative properties to the synthetic Aβ and can be used in downstream biological experiments. Finally, we developed new pH-activable probes to visualize intracellular organelles in glia. Together, these tools have allowed us to answer questions related to glial functions in the context of neurodegeneration.