The role of clusterin in amyloid-β-associated neurodegeneration.
The role of clusterin in amyloid-β-associated neurodegeneration.
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DOI：
10.1001/jamaneurol.2013.4560
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发表时间：
2014-02
期刊：
影响因子：
29
通讯作者：
Dale, Anders M.
中科院分区：
文献类型：
--
作者：
Desikan, Rahul S.;Thompson, Wesley K.;Holland, Dominic;Hess, Christopher P.;Brewer, James B.;Zetterberg, Henrik;Blennow, Kaj;Andreassen, Ole A.;McEvoy, Linda K.;Hyman, Bradley T.;Dale, Anders M.
聚集的证据表明，簇蛋白，伴侣糖蛋白，影响阿尔茨海默病（AD）的神经变性。然而，clusterin在AD发病机制中的确切作用仍不清楚。阐明非痴呆老年人中随时间推移聚集蛋白、β淀粉样蛋白（Aβ）、p-tau蛋白与脑萎缩率之间的关系。一个认知正常的老年参与者（HC）和轻度认知障碍（MCI）个体的纵向队列，通过基线腰椎穿刺和纵向结构MRI进行评估。遍布美国和加拿大的研究中心。我们检查了241名非痴呆老年人（91名参与者的临床痴呆评分（CDR）为0，150名参与者的CDR为0.5）。采用线性混合效应模型，我们研究了CSF clusterin、CSF Aβ1-42和CSF p-tau 181 p之间的相互作用对内嗅皮层和海马萎缩率的影响。在所有受试者中，我们发现CSF clusterin和CSF Aβ1-42在内嗅皮质萎缩率上存在显著的相互作用，但在海马萎缩率上没有。CSF聚集素与CSF Aβ1-42阳性者的内嗅皮质萎缩率相关，而与CSF Aβ1-42阴性者的内嗅皮质萎缩率无关。在二次分析中，我们发现CSF Aβ1-42和CSF clusterin以及CSF Aβ1-42和CSF p-tau 181 p在内嗅皮质萎缩率上存在显著的相互作用。我们在MCI和HC队列的亚组分析中发现了相似的结果。在非痴呆的老年人中，Aβ相关的体积损失发生在存在升高的丛生蛋白的情况下。丛生蛋白对Aβ相关脑萎缩的作用不受p-tau混淆或解释。这些发现暗示了clusterin在AD神经退行性过程的最早阶段中的潜在重要作用，并表明clusterin和p-tau对Aβ相关体积损失的独立作用。
Converging evidence indicates that clusterin, a chaperone glycoprotein, influences Alzheimer's disease (AD) neurodegeneration. However, the precise role of clusterin in AD pathogenesis is still not well understood. To elucidate the relationship between clusterin, amyloid-β (Aβ), p-tau, and rate of brain atrophy over time among non-demented older individuals. A longitudinal cohort of cognitively normal older participants (HC) and individuals with mild cognitive impairment (MCI) assessed with baseline lumbar puncture and longitudinal structural MRI. Research centers across the United States and Canada. We examined 241 non-demented older individuals (91 participants with a Clinical Dementia Rating (CDR) of 0 and 150 individuals with a CDR of 0.5). Using linear mixed effects models, we investigated interactions between CSF clusterin, CSF Aβ1-42 and CSF p-tau181p on atrophy rate of the entorhinal cortex and hippocampus. Across all participants, we found a significant interaction between CSF clusterin and CSF Aβ1-42 on entorhinal cortex atrophy rate, but not on hippocampal atrophy rate. CSF clusterin was associated with entorhinal cortex atrophy rate among CSF Aβ1-42 positive individuals, but not among CSF Aβ1-42 negative individuals. In secondary analyses, we found significant interactions between CSF Aβ1-42 and CSF clusterin and CSF Aβ1-42 and CSF p-tau181p on entorhinal cortex atrophy rate. We found similar results in subgroup analyses within the MCI and HC cohorts. In non-demented older individuals, Aβ-associated volume loss occurs in the presence of elevated clusterin. The effect of clusterin on Aβ-associated brain atrophy is not confounded or explained by p-tau. These findings implicate a potentially important role for clusterin in the earliest stages of the AD neurodegenerative process and suggest independent effects of clusterin and p-tau on Aβ-associated volume loss.
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影响因子：
--
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
通讯作者：
Lovestone, Simon
DOI：
10.3174/ajnr.a3267
发表时间：
2013-03
期刊：
AJNR. American journal of neuroradiology
影响因子：
--
作者：
Desikan RS;McEvoy LK;Holland D;Thompson WK;Brewer JB;Aisen PS;Andreassen OA;Hyman BT;Sperling RA;Dale AM;Alzheimer's Disease Neuroimaging Initiative
通讯作者：
Alzheimer's Disease Neuroimaging Initiative
影响因子：
10.9
作者：
Holland, Dominic;Dale, Anders M.
通讯作者：
Dale, Anders M.
影响因子：
11.2
作者：
Desikan, Rahul S.;McEvoy, Linda K.;Thompson, Wesley K.;Holland, Dominic;Roddey, J. Cooper;Blennow, Kaj;Aisen, Paul S.;Brewer, James B.;Hyman, Bradley T.;Dale, Anders M.
通讯作者：
Dale, Anders M.
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