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2015 Grants - Crary
Neuropathological Characterization of Primary Age-Related Tauopathy
John Fonda Crary, M.D., Ph.D.
Icahn School of Medicine at Mount Sinai
New York, New York
2015 New Investigator Research Grant
Can the accumulation of abnormal tau protein in the brain lead to disorders that are distinct from Alzheimer’s disease?
Two hallmark brain changes associated with Alzheimer’s disease are the accumulation of beta-amyloid protein fragments into amyloid “plaques” and the accumulation of abnormal tau protein into neurofibrillary “tangles.” Research has shown that abnormal tau protein may also accumulate in other types of neurodegenerative disease. Normally, tau helps maintain the structure of nerve cells in the brain. Abnormal tau loses its ability to carry out this vital function and accumulates into tangles, which are believed to be toxic to nerve cells. Recent studies suggest that many tau diseases (“tauopathies”) exist — and that some may be related to Alzheimer’s disease and others may not. Thus, there is a need to better characterize the distinct ways that abnormal tau can affect brain health.
John Fonda Crary, M.D., Ph.D., and colleagues have recently proposed criteria for a newly identified kind of tau disease termed “primary age-related tauopathy” (PART). People with PART have neurofibrillary tangles in their brains but do not have the amyloid plaques characteristic of Alzheimer’s disease. In the past, scientists have considered such symptoms to represent an early stage of Alzheimer’s. Dr. Crary’s team, however, has found that PART may be distinct from early Alzheimer’s disease. For example, people with PART may develop dementia, but they do not experience the severe, Alzheimer’s-related functional impairments — such as the inability to bathe, eat or carry out other vital daily activities. Moreover, people with PART appear to have genes that protect them from amyloid plaques while making them unusually susceptible to neurofibrillary tangles.
For their current grant, Dr. Crary and his team plan to verify PART as a distinct neurological disease by analyzing brain samples from a large group of people who had neurological symptoms characteristic of either PART or Alzheimer’s. They will characterize in detail the structural and molecular brain changes associated with PART. They will also determine if there are genetic differences in the people with brain changes associated with PART versus the people with brain changes associated with Alzheimer’s.
The results of this work could improve our understanding of how abnormal tau affects the aging brain. These findings may also shed new light on genetic risk factors that underlie Alzheimer’s and other related dementias. Most importantly, these findings may help enable the development of novel therapeutic strategies that target abnormal tau for the treatment of many neurodegenerative diseases.