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Keck School team identifies new model to study Alzheimer’s disease

A team led by Terrence Town used genetically engineered rats to find new clues about Alzheimer's disease. (Photo/Courtesy of Keck School)

Research by Keck School of Medicine of USC faculty supports the idea that increases in a molecule called beta-amyloid in the brain drives Alzheimer’s disease, according to a study published in The Journal of Neuroscience.

Using genetically engineered lab rats with the full array of brain changes associated with Alzheimer’s disease, a team led by Terrence Town, the study’s senior author and professor in the Department of Physiology and Biophysics at the Zilkha Neurogenetic Institute, created a next-generation disease model to study the disease.

“We believe the rats will be an excellent, stringent pre-clinical model for testing experimental Alzheimer’s disease therapeutics,” said Town, who conducted the study while working as a professor of biomedical sciences at Cedars-Sinai Medical Center and the David Geffen School of Medicine at the University of California, Los Angeles.

Alzheimer’s is an age-related brain disorder that gradually destroys a person’s memory, thinking and the ability to carry out simple tasks.

Affecting at least 5.1 million Americans, the disease is the most common form of dementia in the United States. Pathological hallmarks of Alzheimer’s brains include abnormal levels of beta-amyloid protein that form amyloid plaques; tau proteins that clump together inside neurons and form neurofibrillary tangles; and neuron loss. In addition, glial cells — which normally support, protect or nourish nerve cells — are overactivated in Alzheimer’s.

Using rats engineered to have certain mutant genes, the researchers were able to see that beta-amyloid in the rats’ brains increased with age. They also noticed the development of neurofibrillary tangles in brain regions most affected by Alzheimer’s involving learning and memory, and the death of about 30 percent of neurons, or brain cells, in these regions. Some of the rats’ glial cells acquired shapes reminiscent of the activated glia found in patients.

Activation of glia occurred earlier than amyloid plaque formation, which suggests Town and his colleagues identified an early degenerative event and a new treatment target that scientists studying other rodent models may have missed.

In addition to grants from the National Institute of Health’s National Institute of Neurological Disorders and Stroke (grant number NS076794), National Institute on Aging (AG029726, AG033394) and the National Institutes of Mental Health Intramural Research Program, this study was funded by the Alzheimer’s Association (IIRG-05-14993 and ZEN-10-174633) and the Ellison Foundation/American Federation for Aging Research (M11472).

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Keck School team identifies new model to study Alzheimer’s disease

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