| 27-Dec-2004 - Researchers produce
robust tau aggregation in human cells
(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.
Full Release - http://www.mayoclinic.org/news2004-jax/2544.html
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