Preclinical Assessment of Young Blood Plasma for Alzheimer Disease.
Preclinical Assessment of Young Blood Plasma for Alzheimer Disease.
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DOI：
10.1001/jamaneurol.2016.3185
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发表时间：
2016-11-01
期刊：
影响因子：
29
通讯作者：
Wyss-Coray T
中科院分区：
文献类型：
--
作者：
Middeldorp J;Lehallier B;Villeda SA;Miedema SS;Evans E;Czirr E;Zhang H;Luo J;Stan T;Mosher KI;Masliah E;Wyss-Coray T
阿尔茨海默病（AD）的病理学早在临床症状出现之前就开始了，并且没有治疗，延迟或预防该疾病的疗法。2只小鼠之间的共享血液循环（又名联体共生）或重复注射年轻血浆（2至3个月大的小鼠的血浆）到老年小鼠中，揭示了年轻血浆对突触功能和行为的益处。然而，据我们所知，年轻血液的潜在益处尚未在神经变性或AD的临床前模型中进行测试。确定年轻血浆是否改善AD小鼠模型的病理和认知，并可能成为该疾病未来的治疗方法。在这项临床前研究中，携带导致家族性AD的人类突变APP基因的小鼠被老化以发展AD样疾病，包括淀粉样斑块的积累、突触和神经元蛋白的丢失以及行为缺陷。最初的共生研究于2010年完成，最终研究于2014年进行。然后通过手术将阿尔茨海默病模型小鼠与年轻的健康小鼠连接，从而通过共生提供共享的血液循环，或者通过重复注射年轻小鼠的血浆来治疗阿尔茨海默病模型小鼠。评估神经病理学参数和海马基因表达对治疗的响应变化。此外，在静脉注射年轻血浆的AD模型小鼠中测试认知。患有疾病的老年突变淀粉样蛋白前体蛋白小鼠在联体生活中暴露于年轻血液后（突触素P = .02;钙结合蛋白P =.02）或静脉内血浆给药后（突触素P < .001;钙结合蛋白P = .14），突触和神经元蛋白水平几乎完全恢复。淀粉样蛋白斑块不受影响，但海马神经元的有益作用伴随着异常细胞外受体激酶信号传导的逆转（P = .05），这是一种与AD有关的激酶。此外，年轻血浆给药与淀粉样前体蛋白小鼠的工作记忆（P = 0.01）和联想记忆（P = 0.02）改善相关。年轻血液中的因子有可能改善AD模型中的疾病。
Alzheimer disease (AD) pathology starts long before clinical symptoms manifest, and there is no therapy to treat, delay, or prevent the disease. A shared blood circulation between 2 mice (aka parabiosis) or repeated injections of young blood plasma (plasma from 2- to 3-month-old mice) into old mice has revealed benefits of young plasma on synaptic function and behavior. However, to our knowledge, the potential benefit of young blood has not been tested in preclinical models of neurodegeneration or AD. To determine whether young blood plasma ameliorates pathology and cognition in a mouse model for AD and could be a possible future treatment for the disease. In this preclinical study, mice that harbor a human mutant APP gene, which causes familial AD, were aged to develop AD-like disease including accumulation of amyloid plaques, loss of synaptic and neuronal proteins, and behavioral deficits. The initial parabiosis studies were done in 2010, and the final studies were conducted in 2014. Alzheimer disease model mice were then treated either by surgically connecting them with a young healthy mouse, thus providing a shared blood circulation through parabiosis, or through repeated injections of plasma from young mice. Neuropathological parameters and changes in hippocampal gene expression in response to the treatment were assessed. In addition, cognition was tested in AD model mice intravenously injected with young blood plasma. Aged mutant amyloid precursor protein mice with established disease showed a near complete restoration in levels of synaptic and neuronal proteins after exposure to young blood in parabiosis (synaptophysin P = .02; calbindin P = .02) or following intravenous plasma administration (synaptophysin P < .001; calbindin P = .14). Amyloid plaques were not affected, but the beneficial effects in neurons in the hippocampus were accompanied by a reversal of abnormal extracellular receptor kinase signaling (P = .05), a kinase implicated in AD. Moreover, young plasma administration was associated with improved working memory (P = .01) and associative memory (P = .02) in amyloid precursor protein mice. Factors in young blood have the potential to ameliorate disease in a model of AD.
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影响因子：
82.9
作者：
Nagahara AH;Merrill DA;Coppola G;Tsukada S;Schroeder BE;Shaked GM;Wang L;Blesch A;Kim A;Conner JM;Rockenstein E;Chao MV;Koo EH;Geschwind D;Masliah E;Chiba AA;Tuszynski MH
通讯作者：
Tuszynski MH
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
25
作者：
Palop, Jorge J.;Mucke, Lennart
通讯作者：
Mucke, Lennart
影响因子：
1.7
作者：
Perry, G;Roder, H;Smith, MA
通讯作者：
Smith, MA
影响因子：
4.2
作者：
Rockenstein, E;Mallory, M;Masliaha, E
通讯作者：
Masliaha, E