Single-synapse analyses of Alzheimer's disease implicate pathologic tau, DJ1, CD47, and ApoE.
Single-synapse analyses of Alzheimer's disease implicate pathologic tau, DJ1, CD47, and ApoE.
复制标题
DOI：
10.1126/sciadv.abk0473
复制
发表时间：
2021-12-17
期刊：
影响因子：
13.6
通讯作者：
Montine TJ
中科院分区：
文献类型：
--
作者：
Phongpreecha T;Gajera CR;Liu CC;Vijayaragavan K;Chang AL;Becker M;Fallahzadeh R;Fernandez R;Postupna N;Sherfield E;Tebaykin D;Latimer C;Shively CA;Register TC;Craft S;Montine KS;Fox EJ;Poston KL;Keene CD;Angelo M;Bendall SC;Aghaeepour N;Montine TJ
来自阿尔茨海默病大脑多个区域的多重单突触事件揭示了人类独有的新变化。突触分子表征在阿尔茨海默病（AD）中是有限的。我们新发明的基于质量细胞术的方法，飞行时间突触测量（SynTOF），用于测量来自无病理改变或纯AD或路易体病（LBD），非人灵长类动物（NHPs）和PS/APP小鼠的约1700万个单突触事件中的38个抗体探针。人类和NHP的突触分子完整性相似。虽然在人类突触中未检测到，但在PS/APP小鼠的单突触事件中存在Aβ。人类突触的聚类和模式鉴定显示出预期的疾病特异性差异，如阿尔茨海默病患者海马病理tau增加，LBD患者尾状多巴胺转运蛋白减少，并揭示了先前未发现的发现，包括阿尔茨海默病患者海马CD47增加，DJ1降低，阿尔茨海默病患者痴呆患者ApoE升高。我们的结果得到了完整组织的多重离子束成像的独立支持。这突出了通过SynTOF获得的神经退行性疾病的更高深度和广度的见解。
Multiplex single-synapse events from multiple regions of Alzheimer’s disease brain revealed new alterations unique to humans. Synaptic molecular characterization is limited for Alzheimer’s disease (AD). Our newly invented mass cytometry–based method, synaptometry by time of flight (SynTOF), was used to measure 38 antibody probes in approximately 17 million single-synapse events from human brains without pathologic change or with pure AD or Lewy body disease (LBD), nonhuman primates (NHPs), and PS/APP mice. Synaptic molecular integrity in humans and NHP was similar. Although not detected in human synapses, Aβ was in PS/APP mice single-synapse events. Clustering and pattern identification of human synapses showed expected disease-specific differences, like increased hippocampal pathologic tau in AD and reduced caudate dopamine transporter in LBD, and revealed previously unidentified findings including increased hippocampal CD47 and lowered DJ1 in AD and higher ApoE in AD with dementia. Our results were independently supported by multiplex ion beam imaging of intact tissue. This highlights the higher depth and breadth of insight on neurodegenerative diseases obtainable through SynTOF.
登录
查看更多内容
影响因子：
14.5
作者：
Colom-Cadena, Marti;Pegueroles, Jordi;Lleo, Alberto
通讯作者：
Lleo, Alberto
影响因子：
3.7
作者：
Chen, Yi-Song;Lim, Suh-Ciuan;Chen, Mei-Hsuan;Quinlan, Roy A.;Perng, Ming-Der
通讯作者：
Perng, Ming-Der
影响因子：
2.9
作者：
Baker, Steven Andrew;Gajera, Chandresh R.;Montine, Thomas J.
通讯作者：
Montine, Thomas J.
影响因子：
16.6
作者：
Bae, Eun-Jin;Yang, Na-Young;Song, Miyoung;Lee, Cheol Soon;Lee, Jun Sung;Jung, Byung Chul;Lee, He-Jin;Kim, Seokjoong;Masliah, Eliezer;Sardi, Sergio Pablo;Lee, Seung-Jae
通讯作者：
Lee, Seung-Jae
影响因子：
16.6
作者：
Bayés À;Collins MO;Reig-Viader R;Gou G;Goulding D;Izquierdo A;Choudhary JS;Emes RD;Grant SG
通讯作者：
Grant SG