Molecular insights into the pathogenesis of Alzheimer's disease and its relationship to normal aging.
Molecular insights into the pathogenesis of Alzheimer's disease and its relationship to normal aging.
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分子对阿尔茨海默氏病的发病机理及其与正常衰老的关系。
DOI：
10.1371/journal.pone.0029610
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Loboda AP
中科院分区：
文献类型：
--
作者：
Podtelezhnikov AA;Tanis KQ;Nebozhyn M;Ray WJ;Stone DJ;Loboda AP
阿尔茨海默氏病 (AD) 是一种复杂的神经退行性疾病，它通过未知的机制偏离正常的大脑衰老过程。我们分析了 600 多个大脑三个区域的年龄和疾病依赖性基因表达模式的整体结构。基因表达变异几乎可以完全用四种转录生物标志物来解释，我们将其命名为 BioAge（生物年龄）、Alz（阿尔茨海默病）、Inflame（炎症）和 NdStress（神经退行性应激）。 BioAge 捕获了变异的第一个主要组成部分，包括与神经元丢失、神经胶质激活和脂质代谢统计相关的基因。通常，生物年龄随着实际年龄的增长而增加，但在 AD 中，它被过早地表达为好像某些受试者已经 140 岁了。 BioAge 的一个成分 Lipa 含有 AD 危险因子 APOE，反映了脂质代谢的明显早期紊乱。 AD 患者的生物衰老速度无法用 BioAge 来解释，而是与 NdStress 有关，NdStress 包括与蛋白质折叠和代谢相关的基因。炎症由炎症细胞因子和小胶质细胞基因组成，广泛激活并出现在疾病过程的早期。相比之下，疾病特异性生物标志物 Alz 仅选择性地存在于 AD 大脑受影响区域，在发病机制中出现较晚，并且富含与上皮间质 (EMT) 转变过程中信号传导和细胞粘附变化相关的基因。这些生物标志物共同详细描述了衰老过程及其对阿尔茨海默病进展的影响。
Alzheimer's disease (AD) is a complex neurodegenerative disorder that diverges from the process of normal brain aging by unknown mechanisms. We analyzed the global structure of age- and disease-dependent gene expression patterns in three regions from more than 600 brains. Gene expression variation could be almost completely explained by four transcriptional biomarkers that we named BioAge (biological age), Alz (Alzheimer), Inflame (inflammation), and NdStress (neurodegenerative stress). BioAge captures the first principal component of variation and includes genes statistically associated with neuronal loss, glial activation, and lipid metabolism. Normally BioAge increases with chronological age, but in AD it is prematurely expressed as if some of the subjects were 140 years old. A component of BioAge, Lipa, contains the AD risk factor APOE and reflects an apparent early disturbance in lipid metabolism. The rate of biological aging in AD patients, which cannot be explained by BioAge, is associated instead with NdStress, which includes genes related to protein folding and metabolism. Inflame, comprised of inflammatory cytokines and microglial genes, is broadly activated and appears early in the disease process. In contrast, the disease-specific biomarker Alz was selectively present only in the affected areas of the AD brain, appears later in pathogenesis, and is enriched in genes associated with the signaling and cell adhesion changes during the epithelial to mesenchymal (EMT) transition. Together these biomarkers provide detailed description of the aging process and its contribution to Alzheimer's disease progression.
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影响因子：
3.7
作者：
Cao, Kajia;Chen-Plotkin, Alice S.;Wang, Li-San
通讯作者：
Wang, Li-San
DOI：
10.1016/s0140-6736(20)32205-4
发表时间：
2021-04-24
期刊：
Lancet (London, England)
影响因子：
--
作者：
Scheltens P;De Strooper B;Kivipelto M;Holstege H;Chételat G;Teunissen CE;Cummings J;van der Flier WM
通讯作者：
van der Flier WM
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
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
46.9
作者：
Hughes, TR;Mao, M;Linsley, PS
通讯作者：
Linsley, PS