Warning: Illegal string offset 'lang' in /home1/roskampi/public_html/articles/wp-content/plugins/keyword-statistics/keyword-statistics.php on line 350

Warning: Illegal string offset 'keywords' in /home1/roskampi/public_html/articles/wp-content/plugins/keyword-statistics/keyword-statistics.php on line 354

Warning: Illegal string offset 'description' in /home1/roskampi/public_html/articles/wp-content/plugins/keyword-statistics/keyword-statistics.php on line 356

Roskamp Institute Articles Better Science. Real Discovery.

May 8, 2012

A multifaceted role for apoE in the clearance of beta-amyloid across the blood-brain barrier

Filed under: Uncategorized — Tags: — Gogce Crynen @ 12:39 pm

Dr. Bachmeier and Dr. Crawford recently published an article in Neurodegenerative Diseases titled “A multifaceted role for apoE in the clearance of beta-amyloid across the blood-brain barrier”. This report clarifies the role of apoE in the exchange of Aβ across the BBB and describes the contribution of apoE to Aβ accumulation in the AD brain.

Abstract
Background: While apolipoprotein E4 (apoE4) is highly correlated with the development of Alzheimer’s disease (AD), its role in AD pathology and, in particular, beta-amyloid (Aβ) removal from the brain, is not clearly defined. Objective: To elucidate the influence of apoE on the clearance of Aβ across the BBB. Methods: Aβ(1-42) was intracerebrally administered to transgenic mice expressing human apoE isoforms and examined in the periphery. Results: ApoE3 and apoE4 mice had 5-times and 2-times, respectively, more Aβ(1-42) appearing in the plasma than wild-type or apoE knockout mice, indicating an enhanced clearance of Aβ from the brain to the periphery. In vitro, unbound basolateral apoE3 (i.e., not bound to Aβ), and to a lesser extent unbound apoE4, at concentrations ≤10nM facilitated basolateral-to-apical fluorescein-Aβ(1-42) transcytosis across a blood-brain barrier (BBB) model, while apoE isoforms bound to Aβ significantly disrupted Aβ transcytosis. Additionally, following apical exposure to the BBB model, we found apoE4 bound to Aβ is able to penetrate the BBB more readily than apoE3 bound to Aβ and does so via the RAGE transporter. Conclusion: These studies indicate a multifaceted, isoform-dependent role for apoE in the exchange of Aβ across the BBB and may partially explain the association of apoE4 and Aβ brain accumulation in AD.

Powered by WordPress