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2016 Grants - Barthelemy
Quantitative Analyses of Tau Isoforms in Human Brain, CSF, and Plasma by MS
Nicolas Barthelemy, Ph.D.
Washington University in St. Louis
St. Louis, Missouri
2016 Alzheimer’s Association Research Fellowship (AARF)
Can a novel method be used to detect different forms of the tau protein associated with Alzheimer’s disease?
In healthy nerve cells, tau protein helps to maintain cell structure and to transport nutrients throughout the cell. In Alzheimer’s disease, however, tau becomes chemically modified by the addition of phosphate groups (phosphorylation) which can lead to the formation of tau tangles in the brain. Phosphorylation can occur at many different sites on the tau protein, but only some of these lead to harmful changes. To add to this complexity, the tau protein sequence that is phosphorylated comes in at least 6 different versions (isoforms), which may have different abilities to form tau tangles.
Current methods for measuring phosphorylated tau in the brain and cerebrospinal fluid (CSF) are limited in their ability to distinguish between tau isoforms and their specific sites of phosphorylation making it challenging to identify which types of tau are associated with Alzheimer’s disease.
Nicolas Barthelemy, Ph.D. and colleagues have developed a novel, highly sensitive method using mass spectroscopy (MS) to distinguish different tau isoforms and identify where tau has been phosphorylated. Using this new method, the researchers will study brain tissue from individuals who had Alzheimer’s disease and measure how specific sites of tau phosphorylation relate to changes in brain structure and the presence of tau tangles and amyloid plaques. The researchers plan to determine if changes in tau isoforms or phosphorylation patterns can be detected in the blood or CSF at different stages of the disease using this method.
If successful this research may identify novel ways of measuring changes in tau that could serve as tools for the early detection and diagnosis of Alzheimer’s disease. These studies could also inform the development of new therapies targeting tangle formation to help slow or prevent Alzheimer’s disease.