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2008 Grants - Sigurdsson
Tau Pathology: Therapy and In Vivo Imaging
Einar M. Sigurdsson, Ph.D.
New York University School of Medicine
New York, New York
2008 Zenith Fellows Award
One of the hallmarks of Alzheimer's disease is the accumulation in the brain of beta-amyloid, a tiny protein fragment suspected of disrupting cell-to-cell communication and damaging neurons. One promising therapeutic strategy for Alzheimer's is to use vaccination to rid the brain of this protein fragment. Recent clinical trials of a beta-amyloid "vaccine" did show promising early results, such as reductions in beta-amyloid levels. However, the trials had to be prematurely terminated because some participants developed brain inflammation.
Einar M. Sigurdsson, Ph.D., and colleagues have been working to develop a vaccine treatment that targets another hallmark of Alzheimer's disease, the neurofibrillary tangle. This structure is composed mainly of abnormally altered tau protein. In preliminary studies with mice engineered to develop abnormal tau, Dr. Sigurdsson's team has developed antibodies that bind to such tau and slow the protein's accumulation in the brain.
For this proposed grant, the researchers will conduct further studies with mice to refine their antibody treatments. At the same time, they will also test the antibodies' effectiveness on cultured cells. The researchers hope to acquire a better understanding of how the antibodies reduce abnormal tau levels. They also hope to determine which vaccines have the fewest side effects.
In a follow-up investigation, Dr. Sigurdsson's team will study the nerve cells of mice that receive the most effective tau vaccine treatments. The researchers hope to learn how mouse nerve cells are affected by both tau accumulation and the removal of accumulated tau. For this purpose, they will use a newly developed imaging technique called manganese-enhanced magnetic resonance imaging (MEMRI).
Results of this study could lead to more effective and safer vaccine trials. Dr. Sigurdsson's team believes that an optimal vaccination treatment would combine vaccines for tau with improved vaccines for beta-amyloid.