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2018 Alzheimer's Association Research Fellowship (AARF)

Understanding the molecular signature of Tau seeds in the human brain

Can we predict the start of tau protein aggregation in the brain?
 

Simon Dujardin
Massachusetts General Hospital
Boston, MA - United States



Background

Alzheimer’s and other brain diseases is characterized by the accumulation of tau protein into complex structures called neurofibrillary tangles that interfere with nerve cell function and subsequent nerve cell damage. In individual nerve cells in the brain, tau protein is recruited to form tangles in a process called “seeding.” These tangles are thought to start and spread from nerve cell to nerve cell throughout the brain as Alzheimer’s progresses, but the pace of tau movement appears to be different for each individual. Fast tau seeding is linked to more rapid impairment of memory and cognition. Dr. Simon Dujardin will test the idea that different types of tau proteins exist, which have varying capacities to seed new tangles in nerve cells.
 

Research Plan

Dr. Dujardin will examine a large number of human brain samples and samples of the fluid that surrounds the brain (cerebrospinal fluid), and characterize the different types of tau proteins and their ability to seed tangles. The researchers will also explore if the spread of tau can be blocked using antibodies that bind to tau and prevent them from interacting with other tau proteins. Finally, Dr. Dujardin will determine whether it is possible to predict which individuals have a higher propensity for tau spreading and thus more rapid development of neurofibrillary tangles.  Dr. Dujardin hopes to use this information to inform his development that could be used in the clinic to detect tau in cerebrospinal fluid samples from individuals at risk for or with Alzheimer’s.
 

Impact

By identifying tau proteins that have different capacities to form neurofibrillary tangles, these studies may help to explain why the progression of Alzheimer’s and other brain diseases can vary from an individual to individual. This work could potentially lead to the development of new tests to detect early and progressive biological changes.  
 

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