Peripheral complement interactions with amyloid β peptide in Alzheimer's disease: 2. Relationship to amyloid β immunotherapy.
Peripheral complement interactions with amyloid β peptide in Alzheimer's disease: 2. Relationship to amyloid β immunotherapy.
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DOI：
10.1016/j.jalz.2017.04.015
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发表时间：
2018-03
期刊：
影响因子：
--
通讯作者：
Rogers J
中科院分区：
文献类型：
--
作者：
Crane A;Brubaker WD;Johansson JU;Trigunaite A;Ceballos J;Bradt B;Glavis-Bloom C;Wallace TL;Tenner AJ;Rogers J
我们以前的研究表明，淀粉样β肽（Aβ）是受补体介导的清除从外周循环，这一机制是缺乏阿尔茨海默病（AD）。该机制应通过Aβ抗体增强，A β抗体与Aβ形成免疫复合物（IC），因此可能与当前的Aβ免疫治疗方法相关。采用多学科方法证明与单独Aβ相比，红细胞和THP 1衍生巨噬细胞中补体介导的Aβ IC捕获增强。Aβ抗体显著增加Aβ的补体激活和调理作用，随后显著增强人红细胞和巨噬细胞对Aβ的捕获。这些体外结果与非人灵长类动物中静脉给药Aβ IC的外周清除率增强一致。结合我们先前的结果显示外周Aβ清除的AD显著缺陷，本研究结果强烈表明外周机制不应被忽视为Aβ免疫治疗效应的贡献者。
Our previous studies have shown that amyloid β peptide (Aβ) is subject to complement-mediated clearance from the peripheral circulation, and that this mechanism is deficient in Alzheimer’s disease (AD). The mechanism should be enhanced by Aβ antibodies, which form immune complexes (ICs) with Aβ, and therefore may be relevant to current Aβ immunotherapy approaches. Multidisciplinary methods were employed to demonstrate enhanced complement-mediated capture of Aβ ICs compared to Aβ alone in both erythrocytes and THP1-derived macrophages. Aβ antibodies dramatically increased complement activation and opsonization of Aβ, followed by commensurately-enhanced Aβ capture by human erythrocytes and macrophages. These in vitro findings were consistent with enhanced peripheral clearance of intravenously-administered Aβ ICs in non-human primates. Together with our previous results showing significant AD deficits in peripheral Aβ clearance, the present findings strongly suggest that peripheral mechanisms should not be ignored as contributors to the effects of Aβ immunotherapy.
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影响因子：
4.6
作者：
Miles, Luke A.;Crespi, Gabriela A. N.;Doughty, Larissa;Parker, Michael W.
通讯作者：
Parker, Michael W.
针对适当的淀粉样β神经元毒素：阿尔茨海默病免疫治疗的前进之路。
DOI：
10.1186/alzrt272
发表时间：
2014
期刊：
Alzheimer's research & therapy
影响因子：
--
作者：
Goure WF;Krafft GA;Jerecic J;Hefti F
通讯作者：
Hefti F
影响因子：
30.8
作者：
Harold, Denise;Abraham, Richard;Hollingworth, Paul;Sims, Rebecca;Gerrish, Amy;Hamshere, Marian L.;Pahwa, Jaspreet Singh;Moskvina, Valentina;Dowzell, Kimberley;Williams, Amy;Jones, Nicola;Thomas, Charlene;Stretton, Alexandra;Morgan, Angharad R.;Lovestone, Simon;Powell, John;Proitsi, Petroula;Lupton, Michelle K.;Brayne, Carol;Rubinsztein, David C.;Gill, Michael;Lawlor, Brian;Lynch, Aoibhinn;Morgan, Kevin;Brown, Kristelle S.;Passmore, Peter A.;Craig, David;McGuinness, Bernadette;Todd, Stephen;Holmes, Clive;Mann, David;Smith, A. David;Love, Seth;Kehoe, Patrick G.;Hardy, John;Mead, Simon;Fox, Nick;Rossor, Martin;Collinge, John;Maier, Wolfgang;Jessen, Frank;Schuermann, Britta;van den Bussche, Hendrik;Heuser, Isabella;Kornhuber, Johannes;Wiltfang, Jens;Dichgans, Martin;Froelich, Lutz;Hampel, Harald;Huell, Michael;Rujescu, Dan;Goate, Alison M.;Kauwe, John S. K.;Cruchaga, Carlos;Nowotny, Petra;Morris, John C.;Mayo, Kevin;Sleegers, Kristel;Bettens, Karolien;Engelborghs, Sebastiaan;De Deyn, Peter P.;Van Broeckhoven, Christine;Livingston, Gill;Bass, Nicholas J.;Gurling, Hugh;McQuillin, Andrew;Gwilliam, Rhian;Deloukas, Panagiotis;Al-Chalabi, Ammar;Shaw, Christopher E.;Tsolaki, Magda;Singleton, Andrew B.;Guerreiro, Rita;Muehleisen, Thomas W.;Noethen, Markus M.;Moebus, Susanne;Joeckel, Karl-Heinz;Klopp, Norman;Wichmann, H-Erich;Carrasquillo, Minerva M.;Pankratz, V. Shane;Younkin, Steven G.;Holmans, Peter A.;O'Donovan, Michael;Owen, Michael J.;Williams, Julie
通讯作者：
Williams, Julie
影响因子：
--
作者：
Mehta, PD;Pirttilä, T;Wisniewski, HM
通讯作者：
Wisniewski, HM
影响因子：
6
作者：
Bussière, T;Bard, F;Buttini, M
通讯作者：
Buttini, M