Alzheimer disease and the blood brain barrier

Increased production of the amyloid-beta (Abeta) peptide can lead to Abeta aggregation and buildup in the brain and rare familial forms of early onset Alzheimer disease (AD).

Aggregation and buildup of Abeta also appears to contribute to the common, late-onset form of AD, which accounts for 99% of cases, however, there is not strong evidence of Abeta over-production in late-onset AD.

This suggests that there is an age-associated alteration in brain Abeta clearance that contributes to late-onset AD. There is substantial clearance of Abeta from the brain to the blood via the blood-brain-barrier (BBB). Thus, understanding which molecules at the BBB are responsible for Abeta clearance is important. Several transporters have been identified on the BBB that mediate Abeta efflux, however if and how these transporters contribute to Abeta deposition as plaques remain unclear.

In a paper appearing online on October 20 in advance of print publication of the November issue of the Journal of Clinical Investigation, David Holtzman and colleagues from Washington University demonstrate that P-glycoprotein is required for Abeta transport across the BBB and that ablation of this transporter at the BBB increases Abeta deposition in a mouse model of AD.

P-glycoprotein has been a major pharmaceutical target by conferring resistance to many chemotherapy regimens, as well as its role in eliminating a wide variety of medicines via liver uptake. It is possible that chronic treatment with these types of drugs could alter P-glycoprotein function, thereby altering Abeta transport and the risk of developing AD. The findings in this manuscript, in addition to its implications in understanding Abeta transport via the BBB and its therapeutic implications, suggests that researchers should begin to explore whether drugs currently being utilized in humans that affect PgP activity, alter risk for AD.

Comments

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
Post a new comment
Post

While we only use edited and approved content for Azthena answers, it may on occasions provide incorrect responses. Please confirm any data provided with the related suppliers or authors. We do not provide medical advice, if you search for medical information you must always consult a medical professional before acting on any information provided.

Your questions, but not your email details will be shared with OpenAI and retained for 30 days in accordance with their privacy principles.

Please do not ask questions that use sensitive or confidential information.

Read the full Terms & Conditions.

You might also like...
Scientists map molecules within human brain for first time