中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (4): 791-792.doi: 10.4103/1673-5374.322453

• 观点:退行性病与再生 • 上一篇    下一篇

脑缺血是通向阿尔茨海默病的桥梁

  

  • 出版日期:2022-04-15 发布日期:2021-10-16

Brain ischemia as a bridge to Alzheimer’s disease

Ryszard Pluta*   

  1. Laboratory of Ischemic and Neurodegenerative Brain Research, Mossakowski Medical Research Institute, Polish Academy of Sciences, Warsaw, Poland
  • Online:2022-04-15 Published:2021-10-16
  • Contact: Ryszard Pluta, MD, PhD,pluta@imdik.pan.pl.

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摘要： Neural Regen Res：缺血在阿尔茨海默病表型和基因型发展中的作用
    在实验性缺血性脑损伤存活长达 2 年之后，大脑中已记录到弥漫性和老年性淀粉样蛋白斑块。在缺血后，淀粉样蛋白的产生还导致神经变性的进展，通过进行性神经元死亡使缺血的结果恶化。同样在脑缺血后的人类中，在海马和大脑皮层中都观察到了弥漫性和老年性淀粉样蛋白斑块。前期实验表明在存活 2 天的缺血海马 CA1 区，淀粉样蛋白前体基因的表达低于对照值。但是在缺血后 7-30 天，该基因的表达增加到高于对照值。β-分泌酶基因的表达在缺血后 2-7 天高于对照值。相比之下，缺血后 30 天，β-分泌酶基因的表达低于对照值。但是早老素 1 和 2 基因的表达在缺血后 2-7 天高于对照值，缺血后 30 天，低于对照值。最新研究表明在 CA3 区域，缺血后 2、7 和 30 天，淀粉样蛋白前体基因的表达增加到高于对照值。相比之下，α-分泌酶基因的表达在缺血后 2、7 和 30 天降至对照值以下。β-分泌酶基因的表达也低于对照值，但仅在缺血后2-7天。然而，缺血后 30 天，β-分泌酶基因表达增加到高于对照值。早老素1基因表达在缺血后2-7天高于对照值。相比之下，缺血后 30 天，该基因的表达低于对照值。早老素 2 基因表达在缺血后 2-7 天下降，但在缺血后 30 天增加至高于对照值。
  来自波兰科学院的Ryszard Pluta认为缺血后，在海马和大脑皮层的神经元中观察到 tau 蛋白的强烈染色。在缺血后脑中也发现了神经原纤维缠结。在缺血海马CA1区，tau 蛋白基因表达高于对照值共2天，但在缺血后 7-30 天，基因表达低于对照值。在CA3区域，tau 蛋白基因的表达在缺血后2天内下降，但在缺血后7-30天内，基因表达增加到高于对照值。淀粉样蛋白和 tau 蛋白的结合不会导致阿尔茨海默病的发展，缺血可能在阿尔茨海默病中起作用这一事实使少数科学家认为研究应该旨在了解这三个因素之间的相互作用。缺血后大脑中淀粉样蛋白水平的增加会导致淀粉样蛋白在血管壁中积累并伴有原发性动脉粥样硬化，从而导致脑淀粉样血管病的发展。脑淀粉样血管病的发展限制了能量底物通过缺血性血脑屏障向大脑的转运，也减少了大脑中淀粉样蛋白的清除。神经炎症过程中释放的因子会增加血脑屏障的渗漏。血脑屏障通透性的额外增加允许炎症细胞、淀粉样蛋白和 tau 蛋白从循环系统进入大脑，从而导致恶性循环。
    文章在《中国神经再生研究（英文版）》杂志2022年 4 月  4 期发表。


https://orcid.org/0000-0003-0764-1356 (Ryszard Pluta) 

Abstract: An update of the etiology of Alzheimer’s disease (AD): The current theory of the etiology of AD and the guidelines for most of the wide-ranging treatments activities are built around amyloid and tau protein as causative agents of the disease (Atlante et al., 2020). At present, based on a comprehensive evaluation of existing and contemporary studies, important questions arise regarding the causal role of amyloid and tau protein in the pathogenesis of AD (Morris et al., 2018). Analyzes of the available evidence does not allow obvious conclusion that amyloid, and especially tau protein, plays a key role in the etiology of AD (Morris et al., 2018). Evaluation of new data shows that accumulation of amyloid and altered tau protein is not the main cause of AD and more research is needed (Morris et al., 2018). As for the two substances planted to contribute to the development of AD, recent data indicate that the changes of amyloid and tau protein level and structure is triggered by some as yet unspecified factors, and then the triggered amyloid and tau protein interact with each other, exerting synergistic toxic effects on neurons and damaged neurons initiate the development of AD (Morris et al., 2018). It is certain that the pathology of amyloid and tau protein is currently ruled out as the sole cause of the development of dementia, as it cannot explain why about half of the world’s population have accumulation of different kinds of amyloid plaques and neurofibrillary tangles in the absence of dementia (Atlante et al., 2020). In these people, it was observed that the accumulation of neurofibrillary tangles increased exponentially with age (Atlante et al., 2020). In addition, it was noted that the appearance of hippocampus atrophy in elderly people with normal cognitive performance was not dependent on the presence of level and structure of amyloid (Atlante et al., 2020). Moreover, a multicenter study found that in patients diagnosed with AD, about one-third of the cases had no brain amyloid (Atlante et al., 2020).