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

Abstract

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