An international team of scientists has made significant progress in our quest to understand and prevent Alzheimer’s disease. The researchers have managed to recreate the symptoms of the disease in a laboratory, using stem cells.
The study is, in a sense, a testament to just how little scientists know about Alzheimer’s disease.
Based on post-mortem examinations of Alzheimer’s patients, researchers know that two things happen in the brains of those affected by the disease: A plaque called amyloid beta builds up between cells, and tau proteins inside nerve cells become tangled, choking off the cells' normal function.
But which causes which, and is either the cause of the dementia that Alzheimer’s patients experience? That has remained an open question.
Brain Research Can Be Thorny
Researchers haven’t been able to trigger Alzheimer’s disease in laboratory animals because the rodents’ brains seem to be too different from ours. And they can't just open up people's brains to see what's going on inside.
"Originally put forth in the mid-1980s, the amyloid hypothesis maintained that beta-amyloid deposits in the brain set off all subsequent events — the neurofibrillary tangles that choke the insides of neurons, neuronal cell death, and inflammation leading to a vicious cycle of massive cell death,” Rudolph Tanzi, Ph.D., director of the Massachusetts General Hospital Genetics and Aging Research Unit and one of the senior authors of the study, said in a press statement.
“One of the biggest questions since then has been whether beta-amyloid actually triggers the formation of the tangles that kill neurons,” Tanzi added.
3D Model Lets Researchers Test New Drugs
The new research replicated the physical symptoms of Alzheimer’s in a laboratory-developed model brain made from stem cells. Tanzi and his German and South Korean colleagues weren’t the first to use stem cells to try to model Alzheimer's disease. But where others had more or less smeared affected cells across the bottom of a petri dish, this team grew them on a three-dimensional scaffold.
The result was more like a brain, and it developed both amyloid beta plaque buildup and tau tangles. With a working model of the disease in hand, the researchers found that when they slowed amyloid beta buildup, they also prevented the tau tangles from forming. The tangles therefore seem to be a result of the plaque, not vice versa.
Researchers hope the model will improve the process of finding drugs to prevent or treat Alzheimer’s disease. Several drugs that had showed promise in the lab have failed to deliver improvements in real patients. That isn’t surprising, since scientists are still discovering basic facts about the disease pathology.
“With our three-dimensional model that recapitulates both plaques and tangles, we now can screen hundreds of thousands of drugs in a matter of months without using animals in a system that is considerably more relevant to the events occurring in the brains of Alzheimer's patients,” Tanzi said.