Abnormal Presence Of Tau Proteins In Dendritic Spines

Dezhi Liao, PhD University of Minnesota

Co-Principal Investigators

Karen Hsiao Ashe, MD, PhD University of Minnesota


We will test the novel concept that specific chemical modification drives unusual targeting of Alzheimer’s-linked “tau” proteins to the dendritic spines of neurons. This targeting might provide a mechanistic link between amyloid and tauopathies, hallmarks of the Alzheimer’s disease (AD) process. Therefore, the successful completion of this project will provide a more complete mechanistic model for AD than available at present.

Project Details

Alzheimer's disease (AD) is the most common cause of dementia in the elderly, causing gradual memory impairment. What is the culprit for this gradual memory impairment then? The brain is composed of many living units, which are called neurons. Each neuron contains hundreds or thousands of tiny apparatus that are called dendritic spines. If the brain is a computer, and then these dendritic spines serve as numerous storage units like the hard drive or Compact Disc (CD) of typical computers. Two main culprits for the memory loss in AD are two types of proteins: amyloid beta and tau. The co-PI, Dr. Karen Hsiao Ashe, a famous AD scientist, has previously found that a very small change in tau proteins (changing one amino acid from Proline to Leucine) can cause profound memory deficits. In our preliminary studies, we found that this tiny change in the amino acids of tau proteins can drive tau proteins to dendritic spines (right to the memory storage units of the brain!). The proposed project will focus on finding out why these unwelcome guests (tau proteins) frequently go to dendritic spines in AD and how much damage these unwelcome guests can cause. By understanding why, we might be able to develop a novel drug for treating AD by finding a way to block these unwelcome guests from entering our privileged house, the dendritic spine.