Alzheimer's disease risk gene CD33 inhibits microglial uptake of amyloid beta.
Alzheimer's disease risk gene CD33 inhibits microglial uptake of amyloid beta.
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DOI：
10.1016/j.neuron.2013.04.014
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发表时间：
2013-05-22
期刊：
影响因子：
16.2
通讯作者：
Tanzi RE
中科院分区：
文献类型：
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作者：
Griciuc A;Serrano-Pozo A;Parrado AR;Lesinski AN;Asselin CN;Mullin K;Hooli B;Choi SH;Hyman BT;Tanzi RE
跨膜蛋白CD 33是一种唾液酸结合免疫球蛋白样凝集素，调节先天免疫，但在大脑中没有已知的功能。我们以前已经表明，CD 33基因是阿尔茨海默病（AD）的危险因素。在这里，我们观察到AD脑中小胶质细胞中CD 33的表达增加。CD 33 SNP rs3865444的次要等位基因赋予了对AD的保护作用，与AD脑中CD 33表达和不溶性淀粉样蛋白β 42（Aβ42）水平的降低相关。AD患者脑内CD 33免疫反应阳性小胶质细胞数量与不溶性Aβ42水平和斑块负荷呈正相关。CD 33抑制小胶质细胞培养物中Aβ42的摄取和清除。最后，在APPSwe/PS1ΔE9/CD 33 −/−小鼠中，脑内不溶性Aβ42水平以及淀粉样斑块负荷显著降低。因此，CD 33失活可减轻Aβ病理，CD 33抑制可代表AD的一种新疗法。
The transmembrane protein CD33 is a sialic acid-binding immunoglobulin-like lectin that regulates innate immunity but has no known functions in the brain. We have previously shown that the CD33 gene is a risk factor for Alzheimer’s disease (AD). Here, we observed increased expression of CD33 in microglial cells in AD brain. The minor allele of the CD33 SNP rs3865444, which confers protection against AD, was associated with reductions in both CD33 expression and insoluble amyloid beta 42 (Aβ42) levels in AD brain. Furthermore, the numbers of CD33-immunoreactive microglia were positively correlated with insoluble Aβ42 levels and plaque burden in AD brain. CD33 inhibited uptake and clearance of Aβ42 in microglial cell cultures. Finally, brain levels of insoluble Aβ42 as well as amyloid plaque burden were markedly reduced in APPSwe/PS1ΔE9/CD33−/− mice. Therefore, CD33 inactivation mitigates Aβ pathology and CD33 inhibition could represent a novel therapy for AD.
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DOI：
10.1056/nejmoa1211851
发表时间：
2013-01-10
期刊：
The New England journal of medicine
影响因子：
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作者：
Guerreiro R;Wojtas A;Bras J;Carrasquillo M;Rogaeva E;Majounie E;Cruchaga C;Sassi C;Kauwe JS;Younkin S;Hazrati L;Collinge J;Pocock J;Lashley T;Williams J;Lambert JC;Amouyel P;Goate A;Rademakers R;Morgan K;Powell J;St George-Hyslop P;Singleton A;Hardy J;Alzheimer Genetic Analysis Group
通讯作者：
Alzheimer Genetic Analysis Group
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：
5.8
作者：
Jandus, Camilla;Simon, Hans-Uwe;von Gunten, Stephan
通讯作者：
von Gunten, Stephan
影响因子：
4.8
作者：
Lee, C. Y. Daniel;Tse, Wayne;Landreth, Gary E.
通讯作者：
Landreth, Gary E.
影响因子：
30.8
作者：
通讯作者：
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