ALZHEIMER'S DISEASE: MODELING PATHOLOGIC STRAIN-LIKE VARIANTS OF MULTIMERIC A?

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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. There is now strong evidence that Alzheimer's disease is caused by proteins that mistakenly bind to one another to form toxic aggregates in the brain. The protein that drives this process is known as A¿. Little is known about the strains of disease-causing proteins in the living brain. We have developed a new way of causing proteins to aggregate in the brain based on the simple principle that a particular protein molecule with a particular abnormal shape can cause normal versions of the same molecule to become abnormal by a process analagous to seeded crystallization. Recently we have found that molecules that have been developed to image A¿ in Alzheimer's disease may actually distinguish between toxic and benign aggregates of A¿. A¿-binding agents thus have the potential to distinguish among stuctural variants of A¿ that may be differentially toxic to the brain.