http://www.nih.gov/researchmatters/november2014/11032014alzheimer.htm
Alzheimer’s disease is an irreversible, progressive brain disorder. It’s the most common cause of dementia among older people, affecting more than 5 million Americans. The condition, which isn’t a normal part of aging, slowly destroys memory and thinking skills.
To better understand the link between plaques and tangles, a team led by Drs. Rudolph Tanzi and Doo Yeon Kim at Massachusetts General Hospital used a cell culture system to develop a model of Alzheimer’s disease. The research was funded in part by NIH’s National Institute on Aging (NIA) and National Institute of Mental Health (NIMH). The study appeared online on October 12, 2014, in Nature.
The scientists grew human neural stem cells in a 3-D gel culture system. The cells were modified to produce high levels of 2 proteins—beta-amyloid precursor protein and presenilin—with mutations seen in inherited forms of Alzheimer’s disease. Over time, the neural cells secreted beta-amyloid, which formed plaques in the gel matrix. The cells also produced high levels of modified tau, which formed threads in the 3-D culture.
The team found that when they blocked beta-amyloid formation, plaques didn’t develop and levels of the modified tau protein decreased. This indicated that beta-amyloid accumulation contributes to the formation of tangles. When they added a compound that prevents extra phosphate groups from attaching to tau, it prevented the formation of tau tangles, even when amyloid plaques were present.
“In this new system that we call ’Alzheimer’s-in-a-dish,’ we’ve been able to show for the first time that amyloid deposition is sufficient to lead to tangles and subsequent cell death,” Tanzi says.
The cell culture system could potentially be used to screen drugs to prevent or treat Alzheimer’s disease. It might also inform development of cell culture models to study other neurodegenerative disorders.
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