In Vivo Dynamic Movement of Polymerized Amyloid β in the Perivascular Space of the Cerebral Cortex in Mice

Disposition of amyloid beta (A beta) into the perivascular space of the cerebral cortex has been recently suggested as a major source of its clearance, and its disturbance may be involved in the pathogenesis of cerebral amyloid angiopathy and Alzheimer's disease. Here, we explored the in vivo dynamics of A beta in the perivascular space of anesthetized mice. Live images were obtained with two-photon microscopy through a closed cranial window. Either fluorescent-dye-labeled A beta oligomers prepared freshly or A beta fibrils after 6 days of incubation at 37 degrees C were placed over the cerebral cortex. Accumulation of A beta was observed in the localized perivascular space of the penetrating arteries and veins. Transportation of the accumulated A beta along the vessels was slow and associated with changes in shape. A beta oligomers were transported smoothly and separately, whereas A beta fibrils formed a mass and moved slowly. Parenchymal accumulation of A beta oligomers, as well as A beta fibrils along capillaries, increased gradually. In conclusion, we confirmed A beta transportation between the cortical surface and the deeper parenchyma through the perivascular space that may be affected by the peptide polymerization. Facilitation of A beta excretion through the system can be a key target in treating Alzheimer's disease.

Automated summary

This study explored the in vivo dynamics of amyloid beta (Aβ) in the perivascular space of the cerebral cortex in mice. The researchers observed the accumulation of Aβ in the localized perivascular space and found that transportation along the vessels was slow and associated with changes in shape. The study also confirmed the transportation of Aβ between the cortical surface and the deeper parenchyma through the perivascular space.