There is firm evidence from experimental studies and observations on human brains with Alzheimer’s disease that cerebral amyloid angiopathy is a consequence of a failure of clearance of Aβ and interstitial fluid from the brain. In order to test new therapeutic strategies, there is an urgent need for new in vitro models that test the clearance of Aβ. The present study represents a significant step toward efficient in vitro models, as it mimics the walls of large cerebral arteries and the transport of Aβ radially across the wall of the blood vessel into the blood. From an anatomical point of view, the astrocytes are not present in leptomeningeal arteries, but rather leptomeningeal sheets cover the vessels. It is difficult to see how the model could be used to test intramural periarterial drainage of Aβ along the basement membranes of capillaries and arteries. One problem is that transport into the blood occurs at the capillary level, as the LRP transporters are present in the capillary wall and there is no evidence of transport of Aβ across the walls of arteries into the blood. While the endothelial cells used in this model have features of a blood-brain barrier, their umbilical cord origin and the absence of the other cerebral cells such as pericytes most likely result in an extracellular matrix that is not specific to the cerebral vasculature.
Comments
University of Southampton School of Medicine
University of Southampton School of Medicine
There is firm evidence from experimental studies and observations on human brains with Alzheimer’s disease that cerebral amyloid angiopathy is a consequence of a failure of clearance of Aβ and interstitial fluid from the brain. In order to test new therapeutic strategies, there is an urgent need for new in vitro models that test the clearance of Aβ. The present study represents a significant step toward efficient in vitro models, as it mimics the walls of large cerebral arteries and the transport of Aβ radially across the wall of the blood vessel into the blood. From an anatomical point of view, the astrocytes are not present in leptomeningeal arteries, but rather leptomeningeal sheets cover the vessels. It is difficult to see how the model could be used to test intramural periarterial drainage of Aβ along the basement membranes of capillaries and arteries. One problem is that transport into the blood occurs at the capillary level, as the LRP transporters are present in the capillary wall and there is no evidence of transport of Aβ across the walls of arteries into the blood. While the endothelial cells used in this model have features of a blood-brain barrier, their umbilical cord origin and the absence of the other cerebral cells such as pericytes most likely result in an extracellular matrix that is not specific to the cerebral vasculature.
View all comments by Roy WellerMake a Comment
To make a comment you must login or register.