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2019 Alzheimer's Association Research Fellowship to Promote Diversity (AARF-D)

Effect of KIBRA on Tau-Mediated Synaptic and Memory Deficits

What proteins could help prevent damage of nerve cell communication networks during Alzheimer’s dementia?
 

Grant Kauwe, Ph.D.
Buck Institute For Research on Aging
Novato, CA - United States



Background

In a cognitively unimpaired brain, the brain cell’s food transport system is organized in parallel strands like railroad tracks. These tracks allow food and nutrients to travel across the cell, feeding the cells and keeping them healthy. The tau protein helps keep these tracks straight. However, in Alzheimer’s and other brain diseases like frontotemporal dementia, Pick’s disease etc. the shape of tau protein becomes modified leading to tau tangles. Abnormal tau can form toxic tangles that damage nerve cells. Some studies have shown abnormal tau often accumulates in specialized structures called “synapses” that connect one nerve cell to another. Studies show that this can weaken nerve cell communication networks and may contribute to memory loss during Alzheimer’s disease.
 
KIBRA is a protein associated with human memory. Past studies show that people with Alzheimer’s dementia sometimes have low levels of KIBRA in their brains. While the biological mechanism that connects KIBRA levels to memory is not entirely clear, the protein has been identified as being important to synaptic function. More research is needed to understand how KIBRA, abnormal tau, and other proteins work together to change synapses in ways that impairs nerve cell communication in Alzheimer’s.
 

Research Plan

Dr. Grant Kauwe’s team will use genetically engineered Alzheimer’s-like mice to better understand how abnormal tau impacts nerve cell communication through synapses and the relationship KIBRA has to synaptic health. In particular, they will study how tau may change interactions between critical proteins inside synapses.
 
The researchers plan to study brain tissue from the mice that contains abnormal tau inside synapses. Dr. Kauwe will determine whether KIBRA interacts with another protein, called PICK1, inside synapses that contain abnormal tau. Both proteins are important for healthy synapse function and memory. The researchers will also test whether increasing the amount of KIBRA or PICK1 in the Alzheimer’s-like mice can improve synapse function and memory.
 

Impact

The study results could provide insights into ways to restore synapses and nerve cell communication in Alzheimer’s disease. This could lead to new therapies designed to protect nerve cell networks in Alzheimer’s.
 

This project is sponsored by the Alzheimer’s Association, Colorado Chapter.
 

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