Novel Alzheimer’s cell culture model accelerates phenotypic screening

Alzheimer’s disease (AD) is characterized by two pathological hallmarks: amyloid-β (Aβ) plaques and neurofibrillary tangles. However, traditional Alzheimer’s models exhibit either plaques or tangles, but not both. The drugs that appeared to be effective in mice model could turn out ineffective to humans.

Recently, researchers created a novel Alzheimer’s cell culture model which develops both plaques and tangles. This model may accelerate testing of anti-AD compounds. The breakthrough study was published in Nature on October 12[1].

They overexpressed two genes (APP and PSEN1) with familial Alzheimer’s disease mutations to develop neural progenitor cells (神经祖细胞) that produce high levels of Aβ. These stem cells can differentiate into neuronal and glial cells.

The authors grew neurons in a commercially available gel called BD Matrigel. After a few weeks, the cells develop both plaques and tangles that characterize AD. Previously, they had tried to grow the cells in a liquid culture but failed.

Many researchers asked if the amyloid hypothesis was correct after bapineuzumab (anti-Aβ mAb) failed in clinical trials. This paper provides strong support to the amyloid hypothesis. Inhibition of Aβ generation with β-or γ-secretase inhibitors prevents AD in the new model, which is good news.

Although the model lacks certain important components like immune cells which may contribute to the disease, it is a great improvement to the models before.

[1] Nature. 2014, doi: 10.1038/nature13800.

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