Oct 14, 2014

A three-dimensional human neural cell culture model of Alzheimer's disease

Nature
Se Hoon ChoiDoo Yeon Kim

Abstract

Alzheimer's disease is the most common form of dementia, characterized by two pathological hallmarks: amyloid-β plaques and neurofibrillary tangles. The amyloid hypothesis of Alzheimer's disease posits that the excessive accumulation of amyloid-β peptide leads to neurofibrillary tangles composed of aggregated hyperphosphorylated tau. However, to date, no single disease model has serially linked these two pathological events using human neuronal cells. Mouse models with familial Alzheimer's disease (FAD) mutations exhibit amyloid-β-induced synaptic and memory deficits but they do not fully recapitulate other key pathological events of Alzheimer's disease, including distinct neurofibrillary tangle pathology. Human neurons derived from Alzheimer's disease patients have shown elevated levels of toxic amyloid-β species and phosphorylated tau but did not demonstrate amyloid-β plaques or neurofibrillary tangles. Here we report that FAD mutations in β-amyloid precursor protein and presenilin 1 are able to induce robust extracellular deposition of amyloid-β, including amyloid-β plaques, in a human neural stem-cell-derived three-dimensional (3D) culture system. More importantly, the 3D-differentiated neuronal cells expressing FAD mutatio...Continue Reading

  • References29
  • Citations220

References

Mentioned in this Paper

Familial Alzheimer Disease (FAD)
Tauopathies
APP protein, human
Microtubule-Associated Protein 3
Extracellular
Neurofibrillary Degeneration (Morphologic Abnormality)
MAP2 protein, human
Presenilin-1
Presenilin 1, mouse
Neurons

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