Monitoring phagocytic uptake of amyloid β into glial cell lysosomes in real time


Journal article


Priya Prakash*, Krupal P. Jethava*, Nils Korte*, Pablo Izquierdo*, Emilia Favuzzi, Indigo V. L. Rose, Kevin A. Guttenplan, Sayan Dutta, Jean-Christophe Rochet, Gordon Fishell, Shane A. Liddelow, David Attwell, Gaurav Chopra
Chemical Science, 2020

DOI: 10.1039/d1sc03486c

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APA   Click to copy
Prakash*, P., Jethava*, K. P., Korte*, N., Izquierdo*, P., Favuzzi, E., Rose, I. V. L., … Chopra, G. (2020). Monitoring phagocytic uptake of amyloid β into glial cell lysosomes in real time. Chemical Science. https://doi.org/ 10.1039/d1sc03486c


Chicago/Turabian   Click to copy
Prakash*, Priya, Krupal P. Jethava*, Nils Korte*, Pablo Izquierdo*, Emilia Favuzzi, Indigo V. L. Rose, Kevin A. Guttenplan, et al. “Monitoring Phagocytic Uptake of Amyloid β into Glial Cell Lysosomes in Real Time.” Chemical Science (2020).


MLA   Click to copy
Prakash*, Priya, et al. “Monitoring Phagocytic Uptake of Amyloid β into Glial Cell Lysosomes in Real Time.” Chemical Science, 2020, doi: 10.1039/d1sc03486c.


BibTeX   Click to copy

@article{priya2020a,
  title = {Monitoring phagocytic uptake of amyloid β into glial cell lysosomes in real time},
  year = {2020},
  journal = {Chemical Science},
  doi = { 10.1039/d1sc03486c},
  author = {Prakash*, Priya and Jethava*, Krupal P. and Korte*, Nils and Izquierdo*, Pablo and Favuzzi, Emilia and Rose, Indigo V. L. and Guttenplan, Kevin A. and Dutta, Sayan and Rochet, Jean-Christophe and Fishell, Gordon and Liddelow, Shane A. and Attwell, David and Chopra, Gaurav}
}

Abstract

Phagocytosis by glial cells is essential to regulate brain function during development and disease. Given recent interest in using amyloid β (Aβ)-targeted antibodies as a therapy for patients with Alzheimer’s disease, removal of Aβ by phagocytosis is likely protective early in Alzheimer’s disease, but remains poorly understood. Impaired phagocytic function of glial cells surrounding Aβ plaques during later stages in Alzheimer’s disease likely contributes to worsened disease outcomes, but the underlying mechanisms of how this occurs remain unknown. We have developed a human Aβ1-42 analogue (AβpH) that exhibits green fluorescence upon internalization into the acidic phagosomes of cells but is non-fluorescent at physiological pH. This allowed us to image, for the first time, glial uptake of AβpH in real time in live animals. Microglia phagocytose more AβpH than astrocytes in culture, in brain slices and in vivo. AβpH can be used to investigate the phagocytic mechanisms removing Aβ from the extracellular space, and thus could become a useful tool to study Aβ clearance at different stages of Alzheimer’s disease.


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