The formation of neurofibrillary tangles (NFTs) of proteins in the brains of Alzheimer's disease (AD) patients may play an important role in the progression of the disease. These tangles are an accumulation of filaments composed of tau protein. The details of how the tau molecule changes during filament and tangle formation may point to both diagnostic and therapeutic strategies for physicians caring for AD patients.
By marking the brain tissues of deceased AD patients with two antibodies specific to different folded states of the protein, the authors show that the tau protein undergoes a stepwise folding and truncation. The first antibody, Alz-50, appears to mark an early event in the formation of tangles, where one end of the tau molecule folds in on itself. The second antibody, Tau-66, marks a later stage in tangle formation where both ends of the tau protein have been cut off. By using additional markers, the authors found an unambiguous sequence of folding and truncation events in the tau molecule as NFTs are formed.
Dr. Binder received his PhD from Yale University in Biology in 1978 where he worked on microtubule polarity demonstrating that these organelles added subunits from one end more readily than the other. This work represented some of the first papers on microtubule polarity. As a postdoctoral fellow at the University of Virginia, he turned his attention to the neuronal cytoskeleton, publishing the first papers on the subcellular localization of the microtubule-associated protein tau using the first monoclonal antibodies to tau (Tau-1, Tau-2, and Tau-5). This work led to independent collaborations with the Iqbal and Wood laboratories; these studies established Alzheimer's disease neurofibrillary tangles as inclusions containing abnormally phosphorylated tau. Since that time, work from the Binder laboratory has focused on the formation of tau filaments, in vitro and neurofibrillary tangle "evolution" in situ during the course of Alzheimer's disease.
The Associate Editors of the Journal of Alzheimer's Disease select the award recipient from among articles published the previous year's volume. The awardee received the Alzheimer Medal, a 3" bronze medal with the likeness of Alois Alzheimer at the 9th International Conference on Alzheimer's Disease and Related Disorders, Philadelphia, July 17-22, 2004. Former winners include Massimo Tabaton, MD, Thomas Wisniewski, MD, Luciano D'Adamio, MD, PhD, and Suzanne de la Monte, MD, MPH.
This annual award is sponsored by Elan Pharmaceuticals.
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About the Journal of Alzheimer's Disease
The Journal of Alzheimer's Disease (www.j-alz.com) is an international multidisciplinary journal to facilitate progress in understanding the etiology, pathogenesis, epidemiology, genetics, behavior, treatment and psychology of Alzheimer's disease. The journal publishes research reports, reviews, short communications, book reviews, and letters-to-the-editor. The journal is dedicated to providing an open forum for original research that will expedite our fundamental understanding of Alzheimer's disease.
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