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

Priya Prakash, Krupal P. Jethava, Nils Korte, Pablo Izquierdo, Emilia Favuzzi, Indigo V.L. Rose, Kevin A. Guttenplan, Palak Manchanda, Sayan Dutta, Jean Christophe Rochet, Gord Fishell, Shane A. Liddelow, David Attwell, Gaurav Chopra

Research output: Contribution to journalArticlepeer-review

Abstract

Phagocytosis by glial cells is essential to regulate brain function during health and disease. Therapies for Alzheimer's disease (AD) have primarily focused on targeting antibodies to amyloid β (Aβ) or inhibitng enzymes that make it, and while removal of Aβ by phagocytosis is protective early in AD it remains poorly understood. Impaired phagocytic function of glial cells during later stages of AD likely contributes to worsened disease outcome, 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 organelles 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. We find that microglia phagocytose more AβpH than astrocytes in culture, in brain slices and in vivo. AβpH can be used to investigate the phagocytic mechanisms responsible for removing Aβ from the extracellular space, and thus could become a useful tool to study Aβ clearance at different stages of AD. This journal is

Original languageEnglish (US)
Pages (from-to)10901-10918
Number of pages18
JournalChemical Science
Volume12
Issue number32
DOIs
StatePublished - Aug 28 2021

ASJC Scopus subject areas

  • Chemistry(all)

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