Studying the diseases of the brain is a massive challenge for researchers as extracting brain cells, or neurons, from a living patient is difficult and risky. At the same time, examining a patient's brain post-mortem usually only reveals the disease's final stages.
And animal models, while incredibly informative, have frequently fallen short during the crucial drug-development stage of research. But scientists at the Gladstone Institutes and the University of California, San Francisco (UCSF) have taken a potentially more powerful approach: an advanced stem-cell technique that creates a human model of degenerative disease in a dish.
Using this model, the team uncovered a molecular process that causes neurons to degenerate, a hallmark sign of conditions such as Alzheimer's disease and frontotemporal dementia (FTD). The results, published in the latest issue of Stem Cell Reports
, offer fresh ammunition in the continued battle against these and other deadly neurodegenerative disorders.
The research team, led by Gladstone Investigator Yadong Huang, MD, PhD, identified an important mechanism behind tauopathies. A group of disorders that includes both Alzheimer's and FTD, tauopathies are characterized by the abnormal accumulation of the protein Tau in neurons. This buildup is thought to contribute to the degeneration of these neurons over time, leading to debilitating symptoms such as dementia and memory loss. But while this notion has been around for a long time, the underlying processes have largely remained unclear.
"So much about the mechanisms that cause tauopathies is a mystery, in part because traditional approaches—such as post-mortem brain analysis and animal models—give an incomplete picture," explained Dr. Huang, who is also an associate professor of neurology at UCSF, with which Gladstone is affiliated. "But by using the latest stem-cell technology, we generated human neurons in a dish that exhibited the same pattern of cell degeneration and death that occurs inside a patient's brain. Studying these models allowed us to see for the first time how a specific genetic mutation may kick start the tauopathy process."