Harvard Gazette (March 4, 2014): Alzheimer's in a Dish

Publication Date: 
Tue, 03/04/2014

Harvard stem cell scientists have successfully converted skins cells from patients with early onset Alzheimer’s into the types of neurons that are affected by the disease, making it possible for the first time to study this leading form of dementia in living human cells. This may also make it possible to develop therapies more quickly and accurately than before.

The research, led by Tracy Young-Pearse and published in the journal Human Molecular Genetics, confirmed what had long been observed in mouse models: that the mutations associated with early onset Alzheimer’s are directly related to protein cleavage errors that cause a rise in amyloid-beta (Aβ) protein 42, which all people produce but which somehow clumps together to form plaques in Alzheimer’s patients.

“We see this mild increase in Aβ42 in cells from patients with Alzheimer’s disease, which seems to be enough to trigger disease processes,” said Young-Pearse, a Harvard Stem Cell Institute-affiliated faculty member at Brigham and Women’s Hospital. “We also see increases of a smaller species of amyloid-beta called Aβ38, which was unexpected, since it should not be very aggregation-prone. We don’t fully understand what it means, but it may combine with other forms of amyloid-beta to stimulate plaque formation.”

The patient-derived cells also possessed the second hallmark of Alzheimer’s: high amounts of the tau protein, or more accurately tau that has been distorted so that the proteins tangle together. The relationship between amyloid-beta and tau is an ongoing chicken-and-egg debate in Alzheimer’s discussions, with some researchers associating one, the other, or both, with the cause of the disease. 

http://news.harvard.edu/gazette/story/2014/03/alzheimers-in-a-dish/