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2009 Grants - Bacskai
In Vivo Imaging of BBB Integrity to Enable CNS Probe Delivery
Brian J. Bacskai, Ph.D.
Massachusetts General Hospital
2009 Molecular Imaging in Alzheimer's Disease Grant
An important goal of Alzheimer research is the development of methods for imaging amyloid plaques and other features of Alzheimer pathology. A major obstacle toward that goal is the blood-brain barrier (BBB), which carefully controls what compounds in the blood are allowed into the brain. Currently, most imaging dyes that label amyloid plaque or other brain proteins cannot permeate the BBB without the use of other disruptive techniques, which may damage the BBB.
Brian J. Bacskai, Ph.D. and colleagues are studying the BBB and how it functions in aging and Alzheimer's disease, with the goal of developing a general method for introducing imaging dyes into the brain. Although recent research has led to the development of a dye for labeling amyloid plaque in the brain, the method used cannot be applied to other dyes, which are often constructed from antibodies or protein fragments.
Dr. Bacskai's team plans to study the BBB in aging mice and mice that have been genetically altered to express Alzheimer-like pathology. Using established experimental techniques to increase the permeability of the BBB, the researchers will study how aging and the onset of Alzheimer pathology changes the permeability of the BBB to several fluorescent dyes.
Dr. Bacskai and colleagues also plan to study specific dyes that bind to small aggregates of beta-amyloid, a protein fragment that is the major component of amyloid plaques. Together, these studies will advance our understanding of how the BBB functions during aging and in Alzheimer's disease, and they should provide valuable insight into the development of new dyes for imaging brain pathology.