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2019 Zenith Fellows Award Program (ZEN)

TMEM106b as a lysosomal safeguard of cognitive function

Can a gene linked to the body’s waste disposal system help protect the brain?

Joanna Jankowsky, Ph.D.
Baylor College
Houston, TX - United States


A search for genes that may be linked to the cause and progression of dementia has driven dementia research. In recent years, researchers have focused on a gene called TMEM106b. This gene codes for a special protein called transmembrane protein 106b found in lysosomes — compartments inside of brain cells that help degrade and dispose of waste in cells.
Recent studies have found that a variation of the TMEM106b gene may help protect brain function in both healthy older adults and in people with various dementias, including Alzheimer’s. Though it’s unclear exactly how this altered gene form exerts its protective effects, research indicates that it may help lysosomes promote healthy cell-to-cell communication in the brain. Such communication is vital for maintaining memory and other cognitive abilities.

Research Plan

Dr. Joanna Jankowsky and colleagues will study the role of the variation of the TMEM106b gene in lysosomal function and brain health. The researchers will utilize mice that have been genetically engineered to have lower levels or another form of TMEM106b. These mice will include animals with unimpaired memory and mice with impaired memory.
Dr. Jankowsky will then test whether these differences in TMEM106b levels and various forms of TMEM106b affect (1) how the animal brain cells communicate with one another, (2) the overall health of the brain cells, and (3) the ability of both the animals with and without impaired memory to complete cognitive tests.


The results of this study could shed new light on how the function of lysosomes affects the aging brain and the progression of dementia. They could also identify protective TMEM106b as a novel target for future dementia therapies. 

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