Researchers produce robust tau aggregation in human cells

27 December 2004

(Jackonsville, FL) - Researchers at Mayo Clinic in Jacksonville, Fla., have developed a way to create human brain cells in culture that model a key pathology of Alzheimer's disease (AD) and related disorders.

Their cell culture system produces human neuronal cells in which a sufficient quantity of the tau protein aggregates within the cells to form filaments with the physical, chemical and biological characteristics of a group of neurodegenerative disorders collectively called tauopathies.

Their work, published in the November-December issue of the Journal of Alzheimer's Disease, provides researchers with an effective means to determine the role of different mechanisms implicated in the process leading to disease and a cell-based tool to screen potential treatments for AD and other tauopathies.

Despite differences in the clinical signs of AD, Pick's disease, progressive supranuclear palsy, corticobasal degeneration and frontotemporal dementia, the brain dysfunction in each of these diseases is believed to arise from gradual accumulation within brain cells of filamentous aggregates made of tau protein.

Previous studies indicate that a critical concentration of this normally soluble protein is necessary for it to aggregate and form fibrils, which are a pathologic hallmark of all tauopathies. "How this happens is unclear," says Li-Wen Ko, Ph.D., who led the Mayo Clinic research. "But we can better understand the molecular and cellular mechanism underlying such transformation by creating a cell culture model that demonstrates robust tau aggregation. Because human brain cells are the primary target of tauopathies, and abnormalities of these diseases involve accumulation of tau protein in multiple formats, we wanted to grow these cells under a defined culture condition and modify them genetically so that progressive deposition of tau protein in distinct formats can be engineered through separate regulatory mechanisms."

AD, the most familiar tauopathy, is also the most common cause of dementia in the elderly. The disease affects 20 million people worldwide, and its incidence is expected to double over the next 30 years due to the ever-expanding, aging population. Therefore, Ko and his colleagues see the urgent need to understand the mechanism that leads to brain dysfunction in AD patients.