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How does tau protein contribute to Vascular Dementia?
Chenxi Qiu, Ph.D.
Beth Israel Deaconess Medical Center
Boston, MA - United States
Background
Vascular dementia (VaD) is a decline in thinking and other cognitive skills that takes place when blood flow to the brain is impaired. Vascular dementia and Alzheimer’s disease may together constitute a form of “mixed dementia”. However, the exact biological mechanism underlying the link between these two brain disorders is as yet unknown and is an active area of investigation.
Alzheimer’s and other neurodegenerative diseases such as frontotemporal dementia, Pick’s disease etc. is characterized in part, by the accumulation of an abnormal form of the tau protein that forms toxic tau tangles. In preliminary research, Dr. Chenxi Qiu and colleagues have studied the role of tau protein in brain health. Tau is normally modified by a process called phosphorylation (or the addition of a molecule known as phosphate to specific parts on the tau protein. But in Alzheimer’s disease, tau becomes excessively phosphorylated and that tends to clump together into tangles. These tangles have been shown to cause brain cell damage and death. Dr. Qiu and colleagues have identified a particular form of harmful tau, called cis P-tau, that may cause brain damage in early Alzheimer’s disease, well before the formation of tau tangles. In addition, the researchers have found that cis P-tau may be linked to early vascular dementia — a disorder not linked to tau tangles in earlier studies. Based on these findings Dr. Qiu believes that there may be a previously unknown role for tau in the earliest stages of mixed dementias.
Research Plan
Dr. Qiu will study how cis P-tau may contribute to the onset of vascular dementia. First, using brain tissue from people who had VaD and from mice engineered to develop VaD-like brain changes, Dr. Qiu will determine the levels of cis P-tau in these samples. The researchers will then assess how cis P-tau may damage brain blood vessel (tube like structures that help transport blood) cells grown in a laboratory dish; and how it may affect certain cells in the brains of VaD-like mice. Finally, Dr. Qiu will assess whether a drug compound can prevent cis P-tau from damaging cells in the laboratory dish and protect brain cell health and cognitive function in the VaD-like mice.
Impact
The results of this work could shed new light on the potential role of tau in Vascular dementia.
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