Op-Ed: Has Alzheimer’s been recreated in a stem cell lab study?

Posted Oct 18, 2014 by Tim Sandle
According to a newly published report, scientists have used a novel three-dimensional culture method to recreate the plaques and tangles of the neurodegenerative disease Alzheimer’s.
A medical research lab
Growing stem-cell-derived neurons in a gel matrix has enabled biologists to reproduce the hallmarks of Alzheimer’s disease in vitro for the first time. The cell culture model seemingly overcomes several limitations of mouse models and cultured neurons that are commonly used to study the disorder.
Stem cells are undifferentiated biological cells that can differentiate into specialized cells and can divide (through mitosis) to produce more stem cells. Stem cells can be artificially grown and transformed (differentiated) into specialized cell types with characteristics consistent with cells of various tissues such as muscles or nerves. They thus hold great scientific potential.
The reason why scientists are interested in developing a cellular model to study neurodegenerative diseases, rather than simply relying upon animal studies, is because the use of a gel matrix allows neurons to form networks similar to those in the brain. Here, over-expressing genes with Alzheimer’s-linked mutations causes the cells to develop the amyloid plaques and neurofibrillary tangles characteristic of the disease. These complex interactions can be seen far more easily using cells.
Amyloids are insoluble fibrous protein aggregates sharing specific structural traits. These proteins have been associated with the pathology of more than 20 serious human diseases in that abnormal accumulation of amyloid fibrils in organs may lead to amyloidosis, and may play a role in various neurodegenerative disorders, like Alzheimer's. Neurofibrillary tangles are aggregates of hyperphosphorylated tau protein, which is a primary marker of Alzheimer's Disease.
The cell model should make it easier to see why drugs that held the promise to alleviate Alzheimer's disease have been unsuccessful when tried out in mice. In mouse models, researchers have observed either plaques in the brain or tangles, but never both in the same brain. As The New York Times explains, many drug molecules tested in mice have often appeared promising, but then failed in humans. Scientists have been unable to determine why; the stem cell model offers a chance to work out just why experimental drugs have not worked as expected.
The findings have been reported in the journal Nature. The study is titled "A three-dimensional human neural cell culture model of Alzheimer’s disease."
It remains to be seen if stem cells provide the much needed answers to Alzheimer's disease drug development. Hopefully, they will represent a step forwards.