Association of plasma clusterin concentration with severity, pathology, and progression in Alzheimer disease.
Association of plasma clusterin concentration with severity, pathology, and progression in Alzheimer disease.
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DOI：
10.1001/archgenpsychiatry.2010.78
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发表时间：
2010-07
影响因子：
--
通讯作者：
Lovestone, Simon
中科院分区：
文献类型：
--
作者：
Thambisetty, Madhav;Simmons, Andrew;Velayudhan, Latha;Hye, Abdul;Campbell, James;Zhang, Yi;Wahlund, Lars-Olof;Westman, Eric;Kinsey, Anna;Guntert, Andreas;Proitsi, Petroula;Powell, John;Causevic, Mirsada;Killick, Richard;Lunnon, Katie;Lynham, Steven;Broadstock, Martin;Choudhry, Fahd;Howlett, David R.;Williams, Robert J.;Sharp, Sally I.;Mitchelmore, Cathy;Tunnard, Catherine;Leung, Rufina;Foy, Catherine;O'Brien, Darragh;Breen, Gerome;Furney, Simon J.;Ward, Malcolm;Kloszewska, Iwona;Mecocci, Patrizia;Soininen, Hilkka;Tsolaki, Magda;Vellas, Bruno;Hodges, Angela;Murphy, Declan G. M.;Parkins, Sue;Richardson, Jill C.;Resnick, Susan M.;Ferrucci, Luigi;Wong, Dean F.;Zhou, Yun;Muehlboeck, Sebastian;Evans, Alan;Francis, Paul T.;Spenger, Christian;Lovestone, Simon
血液分析物作为阿尔茨海默病 (AD) 病理过程的指标。结合蛋白质组学和神经影像学方法来鉴定与 AD 病理相关的血浆蛋白。发现阶段的蛋白质组学实验旨在鉴定与 AD 病理学相关的血浆蛋白，包括使用神经影像学和更快速的临床进展的萎缩证据，然后使用定量免疫测定进行复制。使用 11C-PiB 淀粉样蛋白成像和具有淀粉样蛋白病理学的转基因小鼠对老年非痴呆人类进行扩展研究。欧洲多中心研究 AddNeuroMed 和美国巴尔的摩老龄化纵向研究 (BLSA)。 AD 患者、轻度认知障碍 (MCI) 受试者和健康对照者进行标准化临床评估和结构神经影像学检查。来自非痴呆老年 BLSA 参与者的血浆样本，通过 PET 进行脑淀粉样蛋白成像。血浆蛋白与脑萎缩、疾病严重程度和临床进展率的关联。对人和转基因小鼠的扩展研究测试了血浆蛋白和脑淀粉样蛋白之间的关联。聚集蛋白/载脂蛋白-J 与 AD 的内嗅皮质萎缩、基线疾病严重程度和快速临床进展相关。聚集蛋白血浆浓度的增加预示着内侧颞叶β淀粉样蛋白（Aβ）负荷增加。患有 AD 的受试者血液中的凝聚素 mRNA 增加，但编码凝聚素 (CLU) 的基因中的 SNP 对基因或蛋白质表达没有影响。最后，APP/PS1 转基因小鼠表现出血浆簇蛋白增加、脑簇蛋白年龄依赖性增加以及淀粉样蛋白和簇蛋白在斑块中的共定位。簇蛋白/载脂蛋白-J 是一种已知的淀粉样蛋白伴侣，与阿尔茨海默病的严重程度、病理学和进展相关。聚集蛋白血浆浓度的增加也与大脑中纤维状 Aβ 负担的增加有关。这些结果证明了簇蛋白在 AD 发病机制中的重要作用，并表明淀粉样蛋白伴侣蛋白的改变可能是阿尔茨海默病的生物学相关外周特征。
Blood-based analytes as indicators of pathological processes in Alzheimer's disease (AD). Combined proteomic and neuroimaging approach to identify plasma proteins associated with AD pathology. Discovery-phase proteomic experiments to identify plasma proteins associated with correlates of AD pathology including evidence of atrophy using neuroimaging and more rapid clinical progression, followed by replication using quantitative immunoassay. Extension studies in older non-demented humans using 11C-PiB amyloid imaging and transgenic mice with amyloid pathology. Multi-center European study, AddNeuroMed, and the Baltimore Longitudinal Study of Aging (BLSA) in United States. AD patients, mild cognitive impairment (MCI) subjects and healthy controls with standardized clinical assessments and structural neuroimaging. Plasma samples from non-demented older BLSA participants with brain amyloid imaging by PET. Association of plasma proteins with brain atrophy, disease severity and rate of clinical progression. Extension studies in man and transgenic mice tested association between plasma proteins and brain amyloid. Clusterin/apolipoprotein-J was associated with atrophy of the entorhinal cortex, baseline disease severity and rapid clinical progression in AD. Increased plasma concentration of clusterin was predictive of greater beta amyloid (Aβ) burden in the medial temporal lobe. Subjects with AD had increased clusterin mRNA in blood but there was no effect of SNPs in the gene encoding clusterin (CLU) with gene or protein expression. Finally, APP/PS1 transgenic mice showed increased plasma clusterin, age-dependent increase in brain clusterin and amyloid and clusterin co-localisation in plaques. Clusterin/apolipoprotein-J is a known amyloid chaperone associated with Alzheimer's disease severity, pathology and progression. Increased plasma concentration of clusterin is also associated with greater burden of fibrillar Aβ in the brain. These results demonstrate an important role of clusterin in the pathogenesis of AD and suggest that alterations in amyloid chaperone proteins may be a biologically relevant peripheral signature of Alzheimer's disease.
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影响因子：
2
作者：
Howlett, D. R.;Bowler, K.;Richardson, J. C.
通讯作者：
Richardson, J. C.
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：
14.5
作者：
Hye, A.;Lynham, S.;Lovestone, S.
通讯作者：
Lovestone, S.
DOI：
10.1073/pnas.162228299
发表时间：
2002-08-06
影响因子：
11.1
作者：
DeMattos, RB;O'dell, MA;Holtzman, DM
通讯作者：
Holtzman, DM
影响因子：
5.1
作者：
Blennow, K;Vanmechelen, E;Hampel, H
通讯作者：
Hampel, H