Authors
Daya Mena, Anna Vincze, Andrew Shultz, Jennifer N Rauch
Published in
Journal of visualized experiments : JoVE. Issue 233. Jul 24, 2026. Epub Jul 24, 2026.
Abstract
As the resident immune cells of the central nervous system, microglia are central regulators of brain homeostasis and key mediators of neurodegenerative disease. These cells continuously survey the neural environment and play a critical role in the recognition, internalization, and degradation of extracellular substrates, including misfolded and aggregated proteins such as pathological tau. Despite growing evidence implicating microglia in tau clearance, existing approaches to measure tau uptake and degradation lack the temporal resolution and sensitivity needed to fully capture these dynamic processes. Here, we developed a luminescence-based assay to quantitatively monitor tau clearance in human induced pluripotent stem cell (iPSC)-derived microglia. This platform leverages a split-luciferase-based complementation system to enable highly sensitive, real-time detection of tau in live cells, allowing for precise tracking of its intracellular processing. This assay is scalable and adaptable across multiple cell types, providing a versatile tool to interrogate endolysosomal pathways and cellular mechanisms governing tau handling in neurodegenerative diseases, including Alzheimer's disease.
PMID:
42574303
Bibliographic data and abstract were imported from PubMed on 11 Aug 2026.
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