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How does tau protein in and around blood vessels affect the brain?
Cristian Lasagna Reeves
Indiana University
Indianapolis, IN - United States
Background
Alzheimer’s and other brain diseases like dementia with Lewy bodies or Frontotemporal dementia is characterized by the accumulation of the protein fragment beta-amyloid in the brain and the formation of complex structures made up of the protein tau that interfere with nerve cell function. In addition, the blood vessels in the brains of individuals with Alzheimer’s often show damage that is thought to further contribute to the development of dementia. In a closely related disease, cerebral amyloid angiopathy (CAA), both beta-amyloid and tau accumulate around the brain’s blood vessels. However, it is not clear what role if any, tau accumulation around blood vessels in CAA has towards impaired nerve cell function and cognitive decline.
Research Plan
Dr. Cristian Reeves plans to examine whether tau accumulation leads to changes in the brain and behavior in CAA. For this study, the researchers plan to use a genetically engineered CAA-like mouse model. Dr. Reeves will use various approaches to track the accumulation of tau around blood vessels in the brain and determine how this accumulation is linked to nerve cell damage and death, as well as to changes in the animals’ memory and cognitive ability over time. The researchers will then determine the effect of blocking the ability of specific cells in the brain to produce tau protein. If tau accumulation around blood vessels is involved in nerve cell death and behavior changes in animals with CAA, then Dr. Reeves will investigate whether blocking tau production reverses these effects.
Impact
Understanding the role of tau in cognitive decline in CAA is expected to provide important insights into how damage to blood vessels in the brain caused by beta-amyloid and tau accumulation contributes to cognitive decline in Alzheimer’s. This work may lead to the development of new therapies to prevent damage to blood vessels in the brain and slow the progression of CAA and Alzheimer’s.
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