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2014 Grants - Perez-Gonzalez
A Pathogenic Role for APP-CTFs-Enriched Exosomes in the Brain
Rocio Perez-Gonzalez, Ph.D.
The Nathan S. Cline Institute for Psychiatric Research
Orangeburg, New York
2014 New Investigator Research Grant
Exosomes are small compartments formed inside cells that release their cargo to the space outside of the cells. They are thought to be involved in several different cellular functions, including biological signaling and disposal of waste products. Scientists also suspect that exosomes may be able to transfer molecules from one cell to nearby cells.
One of the hallmark features of Alzheimer’s disease is the presence of amyloid plaques in the brain, which are largely composed of clumps of the protein fragment beta-amyloid. The cutting of the amyloid precursor protein (APP), creates carboxy-terminal fragments (CTFs) called APP-CTFs from which beta-amyloid is then made. Recent studies using nerve cells grown in laboratory dishes have found exosomes may contain APP-CTFs, but as of yet it has been difficult to study this process in living brain tissue.
Rocio Perez-Gonzalez, Ph.D., and colleagues have developed a novel way to collect exosomes from living brain tissue and have shown that brain exosomes contain large amounts of APP-CTFs. The researchers have proposed to study how exosomes may be involved in the secretion of beta-amyloid from nerve cells and could thus contribute to the movement of beta-amyloid throughout regions of the brain. Dr. Perez-Gonzalez and colleagues plan to study how both nerve cells growing in laboratory dishes and mice genetically altered to have an Alzheimer’s-like condition, are affected by exposure to exosomes containing APP-CTFs. These studies may provide important insights into how beta-amyloid can move throughout the brain, and also may reveal new ways to slow the progression of disease.