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2006 Grant - Baas
Abnormal Microtubule Severing in Alzheimer's Disease
Peter W. Baas, Ph.D.
2005 New Investigator Research Grant
A nerve cell contains long filaments called microtubules, which help to maintaining the complex structure of the cell that is critical for its function. Microtubules also transport nutrients to remote regions of the cell. Although they are important for the cell's structure, microtubules often undergo remodeling, and their assembly and disassembly are carefully controlled by other proteins in the cell.
One such protein is called tau. Tau is believed to protect the microtubules from disassembly. But under appropriate conditions, tau becomes chemically modified by phosphorylation-the addition of phosphate groups to the protein-thereby allowing the microtubule to be disassembled and remodeled.
It has been observed that injured nerve cells from people with Alzheimer's disease are often lacking in microtubules. The cause of this abnormality is not known, but it often occurs even before the development of other well-known features of Alzheimer pathology, such as deposition of amyloid plaques. One clue about why microtubules are lacking in Alzheimer's disease is that tau becomes phosphorylated to a much higher degree than normal.
Peter W. Baas, Ph.D. and colleagues have developed a model of microtubule assembly and disassembly that they propose to explain the loss of micro-tubules in nerve cells from brains affected by Alzheimer's disease. In their model, the unusually high phosphorylation of tau observed in diseased nerve cells allows the microtubules to be disassembled to an unusually high degree, causing the nerve cell to lose much of its structure and function. The researchers will test the different elements of their proposed model by using molecular techniques to modify the presence of tau or its function within mouse nerve cells and then observing microtubule function within those cells.