UCI resarchers create first living model to exhibit

Irvine, Calif. -- A newly engineered, genetically altered mouse will allow researchers for the first time to study the two signature lesions of Alzheimer's disease in a single organism -- a model that closely matches how the disease develops in the human brain. Created by UC Irvine neurobiologists Frank LaFerla and Salvatore Oddo, the mouse is expected to provide a better "living laboratory" for understanding how these lesions grow, aiding efforts to find an effective treatment for both the sporadic and inherited forms of the disease.

"For the first time, plaque and tangle lesion formations can be studied together, letting us understand the relationship between the two lesions and dissect the processes by which they may be connected," said LaFerla, a professor of neurobiology and behavior, and senior author of the study, which appears in the July 31 issue of Neuron.

Plaque lesions grow on the outside of healthy cells, cutting off their ability to communicate with other cells, while tangle lesions grow inside of neural cells and clog signaling pathways. Plaque lesions are factors in the early-onset inherited and sporadic forms of the disease, and tangle lesions are found primarily in the sporadic form.

According to LaFerla, the mouse will be valuable in the search for drugs that can target both lesions. "This may eventually lead to a single class of drugs for treating both the inherited and sporadic forms of the disease," he said. "We now have the ability to study a wider spectrum of Alzheimer's disease than previously possible."

LaFerla and Oddo created the mouse by genetically altering it to host three mutant human genes that foster lesion growth: beta-amyloid precursor protein (APP), presenilin-1 and tau. APP is the source of the beta-amyloid protein that forms into brain plaques, while presenilin-1 is needed for this protein to form. Tau is the critical component of tangles.

Using the triple-transgenic mouse, the UCI researchers hav

Contact: Tom Vasich
University of California - Irvine

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