X-RAY STUDIES OF NEUROFIBRILLARY TANGLES IN ALZHEIMER'S DISEASE BRAIN TISSUE

这个子项目是众多研究子项目之一

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The visible neuronal pathology that occurs in Alzheimer's disease (AD) and a number of other dementia-causing diseases is composed of a polymerized form of the microtubule-binding protein, tau. Collectively, these diseases are termed "tauopathies" and represent the predominant cause of human dementia. This pathology occurs when tau, a molecule that possesses little ordered structure in solution, polymerizes into an apparently well-ordered filament. Tau filaments can take on "straight" (single) or paired helical forms. This self-assembly phenomenon is of interest in its own right as a biophysical process, but this interest is made more acute by the potential relevance of its mechanism to a large number of human neurodegenerative disorders. Similar to the tauopathies (AD, Pick disease, progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), FTDP-17 dementias, and others)(Lee, V., et al Ann. Rev. Neurosci. 24:1121-1159, 2001), aggregation of other proteins by demonstrably similar mechanisms is a characteristic of several other neurodegenerative diseases. Thus, understanding how and why tau polymerizes could open avenues for the development not only of therapeutic agents directed at AD, but at compounds to treat the broader base of neurodegenerative diseases.. Preliminary data taken at Bio-CAT identified diffraction patterns seen previously in purified NFTs, and also identified a number of new structural features, as well as a correspondence between tissue morphology and NFT orientation.