A team from Massachusetts General Hospital (MGH) has created one of the most advanced models of Alzheimer's disease yet, providing researchers with an important tool for developing potential new treatments.
Their "Alzheimer's-in-a-dish" is essentially a culture of human brain stem cells that show signs of neuroinflammation—a key characteristic of the disease that leads to the death of brain cells in patients. For additional accuracy, the culture also incorporates glial cells, which surround and insulate nerve cells in the brain.
The new model, which is described in a Nature Neuroscience paper, builds on the MGH team's previous work: a gel-based cell culture that included two important markers of Alzheimer's development—tangled neurons and amyloid beta plaques.
The build-up of these tangled neurons and plaques of amyloid beta in the brain have been linked to neuroinflammation and the loss of cognitive function seen in sufferers.
"Our original 'Alzheimer's in a dish' system recapitulated the plaques and tangles typically seen in the brains of patients with Alzheimer's disease, but did not induce neuroinflammation," Rudolph Tanzi, director of the Genetics and Aging Research Unit at the MGH Institute for Neurodegenerative Disease (MIND) and co-senior author of the latest paper, said in a statement.
"Studies have shown that we can have many plaques and tangles in our brains with no symptoms, but when neuroinflammation kicks in, exponentially more neurons die and cognitive impairment leading to dementia is induced. A complete model of Alzheimer's pathology needs to incorporate that 'third leg of the stool.'"
To recreate this, the team used recently developed technology created by researchers at the University of North Carolina at Charlotte, known as a "microfluidic" device, which consists of two circular chambers, one inside the other, that are connected by channels. This set-up provided an effective environment for the researchers to model the kind of neuroinflammation seen in Alzheimer's using human brain stem cells that had been modified to have a genetic disposition to the disease.
"This system should help us better understand the timeline by which pathological events lead to dementia and enable us to screen for drugs that stop plaque deposition, tangle formation, and the resultant neuroinflammation," Tanzi said.
Promisingly, with the help of their model, the team found that by blocking two receptors in microglial cells—glial cells that function as nervous system cells—they could prevent neuroinflammation, opening up new opportunities for the discovery of novel drugs.
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Aristos is a Newsweek science reporter with the London, U.K., bureau. He reports on science and health topics, including; animal, ... Read more
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