Deglycosylated anti-Abeta antibody dose-response effects on pathology and memory in APP transgenic mice.
Deglycosylated anti-Abeta antibody dose-response effects on pathology and memory in APP transgenic mice.
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DOI：
10.1007/s11481-008-9114-6
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发表时间：
2008-09
影响因子：
6.2
通讯作者：
Morgan, Dave
中科院分区：
文献类型：
--
作者：
Karlnoski, Rachel A.;Rosenthal, Arnon;Alamed, Jennifer;Ronan, Victoria;Gordon, Marcia N.;Gottschall, Paul E.;Grimm, Jan;Pons, Jaume;Morgan, Dave
关键词：
给淀粉样蛋白沉积转基因小鼠注射抗A-β抗体可以逆转淀粉样蛋白病变，恢复记忆功能。然而，在老年小鼠中，这些治疗也增加了血管渗漏，并促进了血管淀粉样蛋白沉积的形成。与Fc、γ受体和补体亲和力降低的去糖基化抗体与血管淀粉样蛋白和微出血的减少有关，同时保留了天然完整抗体的淀粉样蛋白清除和记忆增强特性。在本实验中，我们研究了3、10或30 mg/kg的脱糖抗体(D-2H6)对老年Tg2576小鼠淀粉样蛋白病理和认知行为的影响。我们发现，在淀粉样前体蛋白(APP)转基因小鼠中，低剂量的脱糖抗体似乎比高剂量更有效地减少病理和记忆丧失。这些数据表明，过多的未与抗原结合的抗体可能通过饱和FcRN抗体转运体而干扰抗体介导的Aβ清除。
Anti-Aβ antibody administration to amyloid-depositing transgenic mice can reverse amyloid pathology and restore memory function. However, in old mice, these treatments also increase vascular leakage and promote formation of vascular amyloid deposits. Deglycosylated antibodies with reduced affinity for Fcγ receptors and complement are associated with reduced vascular amyloid and microhemorrhage while retaining amyloid-clearing and memory-enhancing properties of native intact antibodies. In the current experiment, we investigated the effect of 3, 10, or 30 mg/kg of deglycosylated antibody (D-2H6) on amyloid pathology and cognitive behavior in old Tg2576 mice. We found that low doses of deglycosylated antibody appear more efficacious than higher doses in reducing pathology and memory loss in amyloid precursor protein (APP) transgenic mice. These data suggest that excess antibody unbound to antigen can interfere with antibody-mediated Aβ clearance, possibly by saturating the FcRn antibody transporter.
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