Animal experiments have confirmed the importance of transcytosis in the regulation of cerebral Aβ levels. Five hours after microinjection of 125I-labeled Aβ1–40 into the caudate nucleus, 73.8% of labeled tracer had been found in blood across the BBB in young wild-type mice, while 125I-labeled Aβ1–40 in cerebrospinal fluid (CSF) measured 10.7%, and only 15.6% of the dose remained in the brain parenchyma (Shibata et al., 2000). These findings suggest that endothelial transcytosis by LRP-1 and others is probably one of the most prominent pathways in cerebral Aβ clearance, although this study might underestimate other clearance pathways as all the Aβ peptides found in blood are considered to derive from transcytotic delivery.
