Mechanism of Neuronal versus Endothelial Cell Uptake of Alzheimer's Disease Amyloid β Protein
2009

How Alzheimer's Disease Affects Neurons and Blood-Brain Barrier Cells

publication Evidence: high

Author Information

Author(s): Kandimalla Karunya K., Olenych Scott G., Fulzele Smita, Davidson Michael W., Poduslo Joseph F.

Primary Institution: Florida A&M University

Hypothesis

The study investigates the cellular mechanisms mediating the internalization of Aβ proteins in neurons and BBB endothelial cells.

Conclusion

The study found that Aβ40 is primarily taken up by neurons through non-endocytotic and energy-independent pathways, while BBB endothelial cells internalize it via endocytotic and energy-dependent mechanisms.

Supporting Evidence

  • Aβ40 is preferentially taken up by a subpopulation of cortical and hippocampal neurons.
  • F-Aβ40 showed only partial co-localization with endocytotic markers, suggesting non-endocytotic uptake.
  • Uptake of F-Aβ40 was not significantly affected by conditions that inhibit endocytosis.

Takeaway

This study shows that brain cells can take in a harmful protein in different ways, which helps explain why some brain cells are more affected by Alzheimer's disease than others.

Methodology

The study used laser confocal microscopy and flow cytometry to analyze the uptake of fluorescein labeled Aβ40 in mouse brain slices and differentiated PC12 cells.

Limitations

The study primarily focused on Aβ40 and did not investigate the internalization of Aβ42 in detail due to its oligomeric nature.

Digital Object Identifier (DOI)

10.1371/journal.pone.0004627

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