A 3D human triculture system modeling neurodegeneration and neuroinflammation in Alzheimer's disease

Nat Neurosci. 2018 Jul;21(7):941-951. doi: 10.1038/s41593-018-0175-4. Epub 2018 Jun 27.


Alzheimer's disease (AD) is characterized by beta-amyloid accumulation, phosphorylated tau formation, hyperactivation of glial cells, and neuronal loss. The mechanisms of AD pathogenesis, however, remain poorly understood, partially due to the lack of relevant models that can comprehensively recapitulate multistage intercellular interactions in human AD brains. Here we present a new three-dimensional (3D) human AD triculture model using neurons, astrocytes, and microglia in a 3D microfluidic platform. Our model provided key representative AD features: beta-amyloid aggregation, phosphorylated tau accumulation, and neuroinflammatory activity. In particular, the model mirrored microglial recruitment, neurotoxic activities such as axonal cleavage, and NO release damaging AD neurons and astrocytes. Our model will serve to facilitate the development of more precise human brain models for basic mechanistic studies in neural-glial interactions and drug discovery.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology*
  • Amyloid beta-Peptides / metabolism
  • Astrocytes / metabolism
  • Astrocytes / pathology*
  • Cell Culture Techniques
  • Humans
  • Inflammation / metabolism
  • Inflammation / pathology*
  • Microglia / metabolism
  • Microglia / pathology*
  • Nerve Degeneration / metabolism
  • Nerve Degeneration / pathology*
  • Neurons / metabolism
  • Neurons / pathology*
  • Phosphorylation
  • tau Proteins / metabolism


  • Amyloid beta-Peptides
  • tau Proteins