Authors:

Natalie Kim

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About Paper:

Alzheimer's disease (AD) is an incurable dementia linked to memory loss and cognitive decline. Neurotoxic amyloid-beta oligomers (ABOs) have been found to accumulate in an AD-dependent manner in human brain tissue, CSF, and plasma, induce memory and learning impairment, and instigate key AD hallmarks such as synapse loss and neuronal cell death. Intriguingly, these same ABOs are transiently expressed in the developing CNS. This project focuses on the underlying trafficking mechanisms of ABOs in the developmental embryonic chick model. Recent experiments from the laboratory have found ABOs in extracellular.-vesicles (EVs) isolated from the embryonic retina, suggesting that EVs may have a role in transporting ABOs between cells during neurodevelopment. Here we show that dynamin-dependent endocytosis, a trafficking pathway for EV uptake, is a potential mechanism for cells to release or internalize developmental ABOs. We found that when dynamin-dependent endocytosis is inhibited by the drug Dynasore in embryonic retinal cell cultures, ABO fluorescence signal is distributed non-homogenously across groups of cells in later cell culture ages. Uneven signal distribution suggests that inhibition of dynamin-dependent endocytosis may cause ABO buildup in the cytoplasm by preventing exocytosis after their uptake into cells. Using neurodevelopmental models like embryonic chickens may provide insight into AD, as AB protein sequences found in embryonic chickens and AD humans are identical. Furthermore, experiments on ABO. formation in neurodegeneration suggest that pathological ABOs, like developmental ABOs, may rely on EV-related trafficking pathways to spread and propagate pathology through cell-to-cell communication. We anticipate that these results may highlight key molecules and cell types that participate in developmental ABO trafficking. Understanding ABO trafficking in development would not only reveal novel insights into their role in neurodevelopment, but could potentially reveal underlying ABO trafficking mechanisms that can be therapeutically targeted during AD. OOS OOOOH HOSS OSH SOSH OOH HSS OOOC OOO OOO OHOHCOOSCOOCEOOCOHO

Source:

Northwestern University

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Co-authors:

Natalie Kim