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2022 Alzheimer's Association Research Grant (AARG)

Backbone DegradablePolymer-drug Conjugate for Treatment of AD

Can a new drug delivery system help treat Alzheimer’s by promoting the health of certain brain structures?

Donna Cross, Ph.D.
The University of Utah
Salt Lake City, UT - United States


Within brain cells, tube-shaped structures called microtubules are essential for maintaining cell shape, as well as the shape of connections between brain cells, known as synapses. In some neurodegenerative diseases, including Alzheimer’s and over twenty other brain diseases linked to this biology, microtubules lose their structural integrity and become less stable. Studies have shown that in genetically engineered Alzheimer’s-like mice, using specific proteins to stabilize microtubules could lessen disease-related brain changes. One such stabilizing protein, called paclitaxel (or PTX), has been found to potentially improve memory, reduce brain levels of abnormal tau (a hallmark brain change associated with Alzheimer’s and linked to brain cell damage and death) and prevent brain inflammation in mice.

Research Plan

Dr. Cross and colleagues will test whether a new drug delivery system which can promote microtubule health and prevent brain changes in Alzheimer’s disease. This delivery system, known as a “backbone degradable polymer-drug conjugate”,  uses a protein called angiopep-2 (AP-2), which can transport paclitaxel (PTX) into the brain across the blood brain barrier (a specialized barrier that tightly regulates what goes in and out of the brain from the circulating blood). The researchers will test how well this new delivery system can cross the blood brain barrier in genetically engineered Alzheimer’s-like mice. They will then assess how well the delivery system increases PTX in various areas of the mice brains. Finally, they will determine the effectiveness of PTX treatment in improving microtubule stability, reducing dementia-related brain changes and restoring memory and other brain functions in these disease-like mice.  


Results from this study could clarify our understanding of the roles microtubules play in brain disease. They could also lead to a novel therapeutic approach for treating tau-related dementias at an early stage.

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