Time-dependent Aggregation of β-amyloid Alters Phagocytosis by Human Microglial Cells
Author(s)
Abstract
Alzheimer’s disease is an age-related neurodegenerative disease characterized by the accumulation of extracellular beta-amyloid protein and intracellular tau protein, both of which are correlated to neuronal toxicity. Beta-amyloid peptides are known to self-aggregate after cleavage by β-secretase from smaller oligomerized species into large insoluble plaques. These plaques are a hallmark of Alzheimer’s disease and have been shown to vary in size with increased incubation time. Our interest is focused on the removal of β-amyloid by microglial cells from the brain. Microglia are the brain’s immunological cells that are responsible for the clearance of dysfunctional proteins in the brain as well as acting as key regulators of inflammation in the brain. Our hypothesis stands that as β-amyloid aggregates into larger protein species, phagocytosis decreases due to changes in the peptide structure as well as the increase in size. Phagocytosis was then assessed after exposure via transmission confocal microscopy as well as flow cytometry. Collectively, our data show that β-amyloid phagocytosis decreases with larger β-amyloid aggregates, suggesting methods to disaggregate peptides from large plaques could promote clearance.
Format
Conference Proceeding
Contributor(s)
Faculty Mentor
Min-Ho Kim
Eric Dyne
Modified Abstract

Alzheimer’s disease is an age-related neurodegenerative disorder characterized by the accumulation of extracellular β-amyloid protein and intracellular tau protein. β-amyloid peptides are known to self-aggregate from smaller oligomerized species into large insoluble plaques. As the protein increases in size, the microglia have to target and breakdown a greater amount of material. Therefore, we hypothesized that as β-amyloid aggregation continues, phagocytosis decreases. In order to understand the effect of size on microglial clearance, transmission confocal microscopy and flow cytometry was used. This promoted fragmentation of the β-amyloid large aggregates into a smaller species that induced greater phagocytosis. Overall, microglial size alters the phagocytic capacity of microglial cells, future research direction will focus on disruption of large peptides to restore microglial mediated clearance.
Permalink https://oaks.kent.edu/ugresearch/2020/brain-health-research-institute/time-dependent-aggregation-b-amyloid-alters
Li, S., & Cawood, M. (n.d.). Time-dependent Aggregation of β-amyloid Alters Phagocytosis by Human Microglial Cells (1–). https://oaks.kent.edu/node/10364
Li, Sandy, and Meghan Cawood. n.d. “Time-Dependent Aggregation of β-Amyloid Alters Phagocytosis by Human Microglial Cells”. https://oaks.kent.edu/node/10364.
Li, Sandy, and Meghan Cawood. Time-Dependent Aggregation of β-Amyloid Alters Phagocytosis by Human Microglial Cells. https://oaks.kent.edu/node/10364.