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2024 Alzheimer's Association Research Grant (AARG)

Deep tissue multiphoton imaging of the hippocampus in Alzheimer’s disease

Could a new brain imaging technique measure both amyloid plaques and tau tangles in Alzheimer’s?

Steven Hou, Ph.D.
Massachusetts General Hospital
Boston, MA - United States



Background

The accumulation of amyloid beta and tau proteins to form plaques and tangles, respectively, are two of the hallmark brain changes seen in Alzheimer’s. Currently, an Alzheimer’s diagnosis relies on expensive brain imaging techniques that can only identify the presence of either amyloid plaques or tau tangles, but not both. In their preliminary studies, Dr. Steven Hou and colleagues have developed a special type of molecule called a “fluorophore” that will appear brighter when it physically interacts with both amyloid plaques and tau tangles after it’s exposed to certain types of light.  

Research Plan

For their project, Dr. Hou and the team have developed three fluorophores (HS-84, HS-169, ZW800-1C) that will be studied. They will first use cognitively unimpaired mice to optimize the dose of each fluorophore that is needed for it to be transported to the brain. Then, each fluorophore will be administered to genetically engineered Alzheimer’s-like mice that develop either amyloid plaques or tau tangles, and the researchers will perform advanced brain imaging techniques to measure the amount of the amyloid plaques or tau tangles that are present. Next, the team will perform the same brain imaging techniques on genetically engineered Alzheimer’s-like mice of different ages to study when these fluorophores can be used to monitor the progression of Alzheimer’s.

Impact

If successful, the results of this study may lead to the development of novel methods to simultaneously measure both amyloid plaques and tau tangles. It could also lead to a more cost-effective approach to diagnose and monitor the disease.

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