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Research Grants 2014

To view an abstract, select an author from the vertical list on the left.

2014 Grants - Ikezu

Exosome Pathway as a Novel Therapeutic Target of Tauopathy

Tsuneya Ikezu, M.D., Ph.D.
Boston University
Boston, Massachusetts

2014 Investigator-Initiated Research Grant: Discovery-Validation of Therapeutic Targets for Developing Novel Interventions for Alzheimer’s Disease

Tau protein plays an important role in the development of Alzheimer’s and other neurodegenerative diseases, collectively known as “taupathies.” Tau normally functions to help maintain cell structure but in some brain diseases, it becomes abnormally modified, and can ultimately accumulate to form neurofibrillary tangles, a hallmark feature of Alzheimer’s disease and other taupathies.

Most of the accumulation of tau protein into neurofibrillary tangles occurs inside nerve cells. However, recent evidence suggests that abnormal tau protein may be able to be transported from one nerve cell to nearby cells leading to the movement of abnormal tau through the brain. This finding has important implications for the progression of Alzheimer’s disease, but the mechanisms of this process are not yet understood.

Tsuneya Ikezu, M.D., Ph.D., and colleagues have proposed a series of studies examining the mechanisms underlying the movement of abnormal tau protein throughout the brain. The researchers plan to test the idea that this transport may involve another type of cell found in the brain, known as microglia. Microglia are part of the immune system and are important for capturing and degrading waste proteins and other debris by enveloping them in small compartments known as exosomes, and then releasing them to the outside the cell.

Dr. Ikezu and colleagues suspect that abnormal tau may be encased and released by these microglia exosomes, and then taken up by healthy nerve cells. The researchers will test these ideas using mice that have been genetically altered to have brain changes associated with abnormal tau accumulation in the brain. They will also test novel drugs that may inhibit the movement of tau between cells. These studies may reveal new drug targets for potentially slowing or halting the progressive development of neurofibrillary tangles in taupathies, such as Alzheimer’s.

Alzheimer's Association International Conference | July 16-20, 2017, London, England

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