Expressing Engineered Receptor Domains to Treat Alzheimer's Disease

Paramita Chakrabarty, PhD
University of Florida (Gainesville, FL, United States)


Todd Golde, M.D., Ph.D.
Mayo Clinic Jacksonville
Year Awarded:
Grant Duration:
July 1, 2011 to June 30, 2012
Alzheimer's Disease
Award Amount:
Grant Reference ID:
Award Type:
Postdoctoral Fellowship
Award Region:
US Southeastern

Soluble Toll-Like Receptors: Potential Anti Amyloid Beta Agents


Histopathological evidence establishes a link between neuroinflammation and senile amyloid beta plaques found in the brains of Alzheimer's disease (AD) patients. It has been proposed that continued neuroinflammation causes bystander toxicity and neuronal death in AD patients. Toll-like receptors have been reported to be critical components of the immune system that drives brain inflammation. In this study, we propose to express parts of Toll-like receptors which would still be able to bind and sequester the amyloid beta peptides without causing sustained neuroinflammation. Such engineered receptors may yield promising therapeutic interventions targeting amyloid pathology. Such receptors have been used in mouse models to target systemic diseases like arthritis and tumor therapy.


Inflammation of the brain has been reported to be associated with the development of Alzheimer's disease. Proteins called “Toll-like receptors” are critical components of the immune system that drives brain inflammation. Therefore, Dr. Paramita Chakrabarty and collaborators will express parts of Toll-like receptors in mice with Alzheimer's disease to sequester beta-amyloid protein and prevent brain plaque formation. The mice will be evaluated for changes in cognitive functions, beta-amyloid plaque formation, and the number of immune cells. This treatment is expected to reduce brain inflammation and thus prevent or reduce the severity of disease symptoms. Similar strategies of Toll-like receptor delivery have been used by researchers in cancer and arthritis research. Dr. Chakrabarty's research will help to clarify the role of immunity in Alzheimer's disease and could lead to the development of new therapeutic strategies.
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