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2014 Grants - Boland
Biomarkers of Impaired Lysosomal Flux in Alzheimer’s Disease
Barry Boland, Ph.D.
University College Cork
2014 New Investigator Research Grant
Lysosomes are compartments inside of cells that are specialized to degrade and dispose of waste, such as old proteins and other cellular debris. The rate of breakdown of cellular waste products by lysosomes is known as lysosomal flux. In people with Alzheimer’s disease, lysosomal flux is impaired, and this leads to the accumulation of waste products in the brain, possibly contributing to the damage or death of nerve cells.
Barry Boland, Ph.D., and colleagues have proposed a series of studies to attempt to identify biomarkers of impaired lysosomal function in early stages of Alzheimer’s disease. They will use a combination of approaches involving nerve cells grown in laboratory dishes as well as analyzing samples of the fluid that surrounds the brain (cerebrospinal fluid). For the cells grown in the laboratory, the researchers will determine if specific proteins important in lysosomal flux are abnormally altered when flux is impaired. Once such altered proteins are identified, the research team will test samples of cerebrospinal fluid to determine if these same altered proteins are present in samples from people who have Alzheimer’s disease.
Finally, Dr. Boland’s team will test white blood cells from individuals with Alzheimer’s disease to determine how they respond to conditions that lead to increased lysosomal dysfunction or “lysosomal stress”, with the idea that this response may be linked to an individual’s risk of developing Alzheimer’s disease. Identification of biomarkers of impaired lysosomal flux could form the foundation for development of early diagnostic tests and new treatments for Alzheimer’s disease.