Nat. Neurosci. https://doi.org/10.1038/s41593-018-0175-4 (2018)

The pathogenesis of Alzheimer’s disease (AD) is poorly understood, in part due to the lack of models that recapitulate the disease. In Nature Neuroscience, Cho and colleagues describe a human cell-culture model of neurons, astrocytes and microglia in a three-dimensional microfluidic platform. Neuron and astrocyte cultures derived from human neural progenitor cells transduced with human Aβ precursor protein containing substitutions associated with familial AD reproduce characteristics of AD, such as aggregation of Aβ, production of inflammatory mediators (CCL2, TNF and IFN-γ) and accumulation of phosphorylated tau protein, and induce the activation and recruitment of microglia seeded in distal chambers. The recruited microglia induce the loss of neurons and astrocytes, retraction of neurites and production of mediators of inflammation in a manner dependent on the receptor TLR4. Thus, the model reproduces physiologically relevant interactions in AD.