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2019 Alzheimer's Association Research Grant (AARG)

Glial Control of the Local Neuronal Translatome in Alzheimer's Disease

Do signals from other cells in the brain contribute to harmful changes in nerve cells during Alzheimer’s disease?

Jimena Baleriola Gomez De Pablos, Ph.D.
Achucarro Basque Center for Neuroscience
Leioa, Spain


Nerve cells sense their environment with the help of long, finger-like extensions collectively called neurites that helps nerve cells communicate with each other.  Neurites are also a way nerve cells sense harmful proteins in the brain, such as the beta-amyloid protein that accumulates and forms disease related plaques, a hallmark of Alzheimer’s disease.
Neurites sense small molecules - that are located inside free-floating pouches called “vesicles” – secreted by one of the most common cell type in the brain called glial cells. This can cause local changes in neurite genetics, without affecting the entire nerve cell. Small molecules secreted by glial cells can also influence how neurite genes are decoded and synthesized into proteins, which can be measured by analyzing a neurite’s individual “translatome” or a study of newly formed proteins in the neurite.
When neurites sense harmful beta-amyloid plaques, their translatome changes locally first, and these changes then spread across the nerve cell and can ultimately cause cell death. Scientists are trying to leverage glial cell communication methods, such as vesicles, as a way to interfere with harmful signals regarding beta-amyloid before they are transported in the brain, and thereby preserve nerve cells in Alzheimer’s disease.

Research Plan

Dr. Jimena Baleriola Gomez De Pablos will collect vesicles secreted by glial cells from genetically engineered Alzheimer’s-like mice to unravel how their contents change neurite and nerve cell function. The researchers will analyze proteins inside the vesicles during communication between glial and nerve cells in the presence of beta-amyloid. Dr. De Pablos’ team will then study how the vesicle contents may influence the protein make up of neurite and the nerve cell, overall.
The researchers will also adjust vesicle contents to find ways to prevent harmful local changes in neurites that may contribute to overall nerve cell death. Finally, Dr. De Pablos will introduce these vesicles into Alzheimer’s-like mice to investigate whether manipulating glial communication with nerve cells may delay or slow the progression of Alzheimer’s.


The study may inform biological underpinnings related to the accumulation of the beta-amyloid plaques and identify a potential mechanism to prevent these plaques and other Alzheimer's disease-related brain changes.  

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