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

• DOI: 10.1371/journal.pone.0004627
• Publication Date: 2009-02-26T19:09:49Z
• Authors: Karunya K. Kandim...; Olenych G. Scott; Smita Fulzele; Michael W. Davidson; Joseph F. Poduslo
• Keywords: Internalization

Alzheimer's disease (AD) is characterized by significant neurodegeneration in the cortex and hippocampus; intraneuronal tangles of hyperphosphorylated tau protein; accumulation beta-amyloid (Abeta) proteins 40 42 brain parenchyma as well cerebral vasculature. The current understanding that AD initiated neuronal Abeta due to their inefficient clearance at blood-brain-barrier (BBB), places neurovascular unit epicenter pathophysiology. objective this study investigate cellular mechanisms mediating internalization principle constituents unit, neurons BBB endothelial cells. Laser confocal micrographs wild type (WT) mouse slices treated with fluorescein labeled Abeta40 (F-Abeta40) demonstrated selective protein a subpopulation cortical hippocampal via nonsaturable, energy independent, nonendocytotic pathways. This groundbreaking finding, which challenges conventional belief are internalized receptor mediated endocytosis, was verified differentiated PC12 cells rat primary (RPH) through laser microscopy flow cytometry studies. Microscopy studies have proportion F-Abeta40 or F-Abeta42 RPH located outside endosomal lysosomal compartments, may accumulate without degradation. In contrast, BBME exhibit dependent uptake F-Abeta40, acidic cell organelle, indicative endocytotic uptake. Such phenomenal difference between provide essential clues how various can differentially regulate help explain vulnerability toxicity.