Transcriptomic analysis to identify genes associated with selective hippocampal vulnerability in Alzheimer's disease.
Transcriptomic analysis to identify genes associated with selective hippocampal vulnerability in Alzheimer's disease.
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DOI：
10.1038/s41467-021-22399-3
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发表时间：
2021-04-19
影响因子：
16.6
通讯作者：
Murray ME
中科院分区：
文献类型：
--
作者：
Crist AM;Hinkle KM;Wang X;Moloney CM;Matchett BJ;Labuzan SA;Frankenhauser I;Azu NO;Liesinger AM;Lesser ER;Serie DJ;Quicksall ZS;Patel TA;Carnwath TP;DeTure M;Tang X;Petersen RC;Duara R;Graff-Radford NR;Allen M;Carrasquillo MM;Li H;Ross OA;Ertekin-Taner N;Dickson DW;Asmann YW;Carter RE;Murray ME
在许多神经退行性疾病中可以看到不同脑区的选择性易感性。海马体和皮层在阿尔茨海默病（AD）中是选择性易感的，然而不同大脑区域的受累程度在患者中是不同的。我们对死后组织中神经原纤维缠结的皮质边缘模式进行分类，以捕获极端和代表性的表型。我们结合大量RNA测序和数字病理学来检查阿尔茨海默病的海马易感性。我们鉴定了与海马易感性相关的海马基因表达变化，并利用机器学习鉴定了与AD神经病理相关的基因，包括SERPINA5、RYBP、SLC38A2、FEM1B和PYDC1。进一步的组织学和生化分析表明SERPINA5的表达与大脑中tau的表达有关。我们的研究强调了在疾病中接受人类大脑异质性以识别疾病相关基因表达的重要性。阿尔茨海默病（AD）通常与海马和皮质病理相关，尽管存在海马保留和边缘优势形式。作者使用转录组学分析和神经病理学鉴定与阿尔茨海默病选择性海马易感性相关的基因。
Selective vulnerability of different brain regions is seen in many neurodegenerative disorders. The hippocampus and cortex are selectively vulnerable in Alzheimer’s disease (AD), however the degree of involvement of the different brain regions differs among patients. We classified corticolimbic patterns of neurofibrillary tangles in postmortem tissue to capture extreme and representative phenotypes. We combined bulk RNA sequencing with digital pathology to examine hippocampal vulnerability in AD. We identified hippocampal gene expression changes associated with hippocampal vulnerability and used machine learning to identify genes that were associated with AD neuropathology, including SERPINA5, RYBP, SLC38A2, FEM1B, and PYDC1. Further histologic and biochemical analyses suggested SERPINA5 expression is associated with tau expression in the brain. Our study highlights the importance of embracing heterogeneity of the human brain in disease to identify disease-relevant gene expression. Alzheimer’s disease (AD) is typically associated with hippocampal and cortical pathology, although hippocampal sparing and limbic predominant forms exist. The authors use transcriptomic analysis and neuropathology to identify genes associated with selective hippocampal vulnerability in AD.
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DOI：
10.1093/biostatistics/kxr054
发表时间：
2012-04
期刊：
Biostatistics (Oxford, England)
影响因子：
--
作者：
Hansen KD;Irizarry RA;Wu Z
通讯作者：
Wu Z
影响因子：
9.8
作者：
Allen, Mariet;Carrasquillo, Minerva M.;Funk, Cory;Heavner, Benjamin D.;Zou, Fanggeng;Younkin, Curtis S.;Burgess, Jeremy D.;Chai, High-Seng;Crook, Julia;Eddy, James A.;Li, Hongdong;Logsdon, Ben;Peters, Mette A.;Dang, Kristen K.;Wang, Xue;Serie, Daniel;Wang, Chen;Thuy Nguyen;Lincoln, Sarah;Malphrus, Kimberly;Bisceglio, Gina;Li, Ma;Golde, Todd E.;Mangravite, Lara M.;Asmann, Yan;Price, Nathan D.;Petersen, Ronald C.;Graff-Radford, Neill R.;Dickson, Dennis W.;Younkin, Steven G.;Ertekin-Taner, Nilufer
通讯作者：
Ertekin-Taner, Nilufer
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：
4.7
作者：
Abu-Rustum NR;Zhou Q;Gomez JD;Alektiar KM;Hensley ML;Soslow RA;Levine DA;Chi DS;Barakat RR;Iasonos A
通讯作者：
Iasonos A
影响因子：
48
作者：
Bonda, David J.;Lee, Hyoung-gon;Camins, Antoni;Pallas, Merce;Casadesus, Gemma;Smith, Mark A.;Zhu, Xiongwei
通讯作者：
Zhu, Xiongwei