Plaque Formation Charted in Mouse Model of Alzheimer's

Alzheimer's disease is characterized by plaque lesions that grow on the outside of healthy nerve cells, cutting off their ability to communicate. 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, while tangle lesions are found primarily in the sporadic form. So far, three mutant human genes have been identified that foster lesion growth: beta-amyloid precursor protein (betaAPP), presenilin-1 and tau. BetaAPP 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.

Investigators at the University of California, Irvine (USA) created a model for the study of Alzheimer's disease by injecting betaAPP and tau genes into single-cell embryos from single-transgenic mice already harboring the presenilin-1 gene. They reported in the July 31, 2003, issue of Neuron that they were able to trace the sequence of plaque development in the brains of the transgenic mice. Beta-amyloid plaques appeared first, and tau-laden tangles appeared later. This suggests that beta-amyloid may be the initiating component of both sporadic and familial Alzheimer's disease.

"This finding confirms the human genetic data indicating that plaques are the earliest pathological feature of the disease,” said senior author Dr. Frank M. LaFerla, professor of neurobiology at the University of California, Irvine. "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.”





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