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Researchers from Harvard Medical School, USA, reported in "Nature Protocols" the characterization of a 3D culture system that exhibits key events in Alzheimer's disease pathogenesis, including extracellular aggregation of β-amyloid and accumulation of hyperphosphorylated tau.
Researchers engineered a commercially available human neural progenitor cell line, ReNcell VM, with lentiviral polycistronic vectors containing mutated familiar Alzheimer's disease genes APP and PSEN1 with GFP or mCherry as reporters to let enrichment of cells with the highest expression levels of FAD genes by fluorescence-activated cell sorting (FACS). FACS sorted cells are maintained as three-dimensional (3D) culture in Matrigel-coated flasks and neuronal differentiation is induced by addition of Heparin and B27 supplements to culture medium. The combination of 3D culture with the over-expression of FAD genes induces extracellular aggregation of amyloid-β (Aβ) in Matrigel and accumulation of hyperphosphorylated/aggregated tau as neurofibrillary tangles. The authors claim that this model can be used to examine the molecular mechanisms underlying the production of high concentrations of Aβ, the accumulation of extracellular Aβ, the deposition of Aβ aggregates, the hyperphosphorylation of tau, and p-tau aggregation. Furthermore, the model can be easily adjusted to be implemented in drug testing and drug screening protocols.
Link to journal page
Reconstitution of amyloid-β aggregates (on the left) and
p-Tau accumulation in cell body and neurites (on the right) of ReN cells.
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