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Do certain forms of the BIN1 protein promote the development of tau tangles in Alzheimer’s disease?
Pierre De Rossi, Ph.D.
The University of Chicago
Chicago, IL - United States
Background
Recent studies have found that certain variations in the gene for bridging integrator-1 (BIN1) may increase risk for Alzheimer’s disease. The BIN1 gene produces several different types or “isoforms” of the BIN1 protein, each of which may have unique functions. Evidence suggests that certain forms of BIN1 are increased in the Alzheimer’s brain and interact with the protein tau. Abnormal tau forms neurofibrillary tangles, one of the hallmark features of the Alzheimer’s brain. More research is needed to better understand the role of BIN1 in the brain and how its interaction with tau may promote brain changes associated with Alzheimer’s disease.
Research Plan
Pierre De Rossi, Ph.D., and colleagues have recently found that one particular form of BIN1 (isoform 9) is increased in brain tissue from people who had Alzheimer’s disease. For their current studies, they have genetically engineered mice to have increased levels of BIN isoform 9 (BIN1iso9) in different cell types in the brain including nerve cells and oligodendrocytes. Oligodendrocytes are a special cell type that surround and insulate the long fibers through which nerve cells communicate. This experimental design will allow the scientists to determine if there are unique cell-specific factors that influence the effect of BIN1ios9 on the brain. The researchers will measure tau accumulation, brain inflammation and nerve cell function in relation to increased levels of BIN1iso9. The mice will also undergo behavioral testing at several time points to detect changes in memory function as they age.
Impact
The results of this work could shed new light on how the interaction of BIN1 and tau proteins in the brain may contribute to the progression of Alzheimer’s. Determining the form of BIN1 that is involved in the disease process will allow scientists to design targeted treatments that could help slow or prevent brain changes associated with Alzheimer’s disease.
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