Heroin abuse exaggerates age-related deposition of hyperphosphorylated tau and p62-positive inclusions.
Heroin abuse exaggerates age-related deposition of hyperphosphorylated tau and p62-positive inclusions.
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DOI：
10.1016/j.neurobiolaging.2015.07.018
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发表时间：
2015-11
影响因子：
4.2
通讯作者：
Keller E
中科院分区：
文献类型：
--
作者：
Kovacs GG;Horvath MC;Majtenyi K;Lutz MI;Hurd YL;Keller E
在阿片类药物滥用者中观察到的过度磷酸化 tau 蛋白水平升高与小胶质细胞激活相关，这被解释为加速阿尔茨海默病 (AD) 相关变化的倾向。本研究重点评估其他神经退行性变相关蛋白，包括 α-突触核蛋白和 TDP-43，以及 p62 阳性沉积物。我们对 27 名有海洛因成瘾记录的个体（年龄：19-40 岁）大脑中的蛋白质沉积进行了系统绘图，并与 11 名对照者（年龄：15-40 岁）进行了比较。我们证实了之前的研究结果，即海洛因成瘾与衰老和 AD 易发脑区的 tau 蛋白过度磷酸化有关。此外，我们发现这种情况也发生在与海洛因滥用相关的分子紊乱和体内神经元网络涉及的区域。然而，不存在β淀粉样蛋白沉积物。我们通过显示 TDP-43 或 α-突触核蛋白病理学的缺乏来扩展先前的发现，并强调药物使用持续时间对年龄相关的 p62 阳性神经炎特征的出现的独立影响。这些观察结果提供了关于年轻海洛因成瘾者大脑神经病理学改变的独特见解，并对大脑衰老以及环境和有毒因素的影响具有影响。
The observation of increased hyperphosphorylated tau levels correlating with microglial activation in opiate abusers has been interpreted as predisposition to accelerated Alzheimer disease (AD)-related changes. The present study focused on evaluating additional neurodegeneration-related proteins, including α-synuclein and TDP-43, and p62-positive deposits. We performed a systematic mapping of protein deposits in the brains of 27 individuals with documented heroin addiction (age: 19-40) and compared with 11 controls (age: 15-40). We confirm previous findings that heroin addiction associates with tau hyperphosphorylation in predilection brain areas for aging and AD. Furthermore, we show that this occurs also in areas implicated in the molecular disturbances and in vivo neuronal networks related to heroin abuse. There was, however, no presence of Amyloid-beta deposits. We extend previous findings by showing the lack of TDP-43 or α-synuclein pathology and emphasize the independent effect of the duration of drug use on the appearance of age-related p62-positive neuritic profiles. These observations provide unique insights about neuropathological alterations in the brains of young heroin addicts and have implications about brain aging and the influences of environmental and toxic factors.