Innate Immune System and Tauopathy
In the first part of the project, the team of Drs. Chakrabarty and Sahara will establish a progression of immune dysfunction in different tau mouse models of Alzheimer’s. The team will use new gene expressing profiling techniques to molecularly “barcode” different immune proteins in these mice, and then use conventional immunohistochemical techniques to measure the expression changes of a select set of proteins. This will allow them to infer whether upregulation of immune signaling precedes disease initiation and can act as a trigger of the disease process. More importantly, such studies can potentially yield a ‘gene signature pattern’ for future tau dementia theragnostics (tests or diagnostic markers that would identify patients who might benefit from a particular therapy).
In the second part of the project, the team of Drs. Chakrabarty and Sahara team will overexpress different inflammatory and anti-inflammatory cytokines in two different tau mouse models, in an effort to test how direct manipulation of the immune system alters tau pathology and neuronal health. Along with monitoring the progression of tau-associated disease by biochemical and histochemical (tissue- and cell-based) methods, the team will use other parameters to measure the outcome—for example, tests for motor and memory impairment in these mice. These studies will: a) enable an unprecedented measurement of the effects of manipulating multiple immune targets in multiple models of tau mice; and b) help to determine which therapies should be developed with high priority.
Finding an effective therapy for AD-type tauopathies is a major unmet medical need. Advances in understanding the root causes of tauopathies have not yet provided disease-modifying therapies that benefit patients suffering from these disorders. The results of this study could help to identify a good target for future treatment, with the potential to leverage existing anti-inflammatory therapies, potentially reducing the time it takes to go from the bench to the clinic. Drs. Chakrabarty and Sahara sincerely thank the BrightFocus Foundation and its partners in sharing our enthusiasm for this proposal.
First published on: July 1, 2013
Last modified on: July 1, 2016