Dr. Krohn and colleagues have identified another Aβ transporter at the CNS-blood barrier, ABCC1. Interestingly, this particular transporter is highly expressed at the choroid plexus, suggesting that, in addition to playing a role at the blood-brain barrier (BBB), it may actively clear Aβ from the CSF as well. Several groups have published BBB Aβ transporters, while CSF-blood transporters have been much less studied. It will be interesting to see how ABCC1 changes in the setting of AD as well as prior to AD (in individuals at risk for AD).

Given some of Dr. Randy Bateman’s recent findings that Aβ clearance is impaired in AD patients, identifying transporters such as this may provide key insights to disease pathogenesis. Dr. Bateman’s studies assessed CSF Aβ clearance in humans; it would be interesting to know the extent to which ABCC1 contributed in those studies. While anti-Aβ therapies may be able to target both production and clearance mechanisms; enhancing ABCC1 transport activity may be a useful target to augment the latter.

View all comments by John Cirrito

This is a great finding. We have all along suspected that there may be a transport mechanism for Aβ through the blood-brain barrier. In our previous article, we thought that impaired clearance of Aβ may be responsible for late-onset AD through impaired transport across the blood-brain barrier or impaired cerebrospinal fluid (CSF) transport (Mawuenyega et al. 2010). However, the evidence was not there to support our speculation. This paper provides what may be one of the missing links in the transport of Aβ through the blood-brain barrier. If this transport is impaired for late-onset AD, that will explain why CSF has low Aβ amounts with respect to high cerebral Aβ accumulation. Mechanisms of increased Aβ production may include alterations in γ- or β-secretase activity; however, there is evidence now showing that impaired clearance definitely leads to cerebral accumulation of Aβ. This article has provided a valuable clue as to prove causality of impaired Aβ clearance for AD, and that is exciting.

View all comments by Kwasi Mawuenyega