患有肝脏病变的饮酒者很少出现α-突触核蛋白病变。

IF 9.3 1区 医学 Q1 CLINICAL NEUROLOGY Acta Neuropathologica Pub Date : 2024-08-01 DOI:10.1007/s00401-024-02772-4
Sylwia Libard, Fredrik Tamsen, Irina Alafuzoff
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引用次数: 0

摘要

有人认为,饮酒可预防帕金森病(PD)。在这里,我们对 100 名死亡年龄在 51 岁至 93 岁之间的受试者的大脑和肝脏死后组织样本进行了评估。其中 20% 的受试者患有痴呆症。我们采用标准化的评估策略来评估大脑和肝脏病变(LP)。我们的研究对象包括因饮酒导致的无肝病、轻度肝病、中度肝病和重度肝病。我们注意到,肝脏脂肪变性与大脑中的α-突触核蛋白(αS)之间的分类数据呈显著负相关,肝脏脂肪变性和纤维化程度与大脑中的αS程度呈显著负相关。观察到的阿尔茨海默氏症 II 型星形胶质细胞与大脑中的αS 病理之间存在明显的负相关。LP与高磷酸化τ(HPτ)之间没有关联。LP的程度与大脑中HPτ、淀粉样β蛋白(Aβ)或转录DNA结合蛋白43(TDP43)的程度之间没有明显的相关性。观察发现,大脑中HPτ、Aβ、αS和TDP43的程度与肝脏脂肪变性、炎症和纤维化之间存在明显的相关性。与无肝硬化或轻度肝硬化的受试者相比,重度肝硬化受试者出现阿尔茨海默氏症II型星形胶质细胞的频率更高。在脑内有阿尔茨海默氏症 II 型星形胶质细胞的受试者中,所评估的蛋白质变化并不更普遍或更严重。在所有病例中,痴呆都是由于蛋白质的综合改变造成的,即混合痴呆,在轻度 LP 患者中,有 30% 的人出现痴呆,而在重度 LP 患者中,只有 13% 的人出现痴呆。总之,我们的研究结果与最近两项荟萃分析得出的结果一致,即有饮酒史的受试者很少发生α-突触核蛋白病。
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Alcohol consumers with liver pathology rarely display α-synuclein pathology

It has been suggested that alcohol consumption protects against Parkinson's disease (PD). Here we assessed postmortem tissue samples from the brains and livers of 100 subjects with ages at death ranging from 51 to 93. Twenty percent of these subjects were demented. We used standardized assessment strategies to assess both the brain and liver pathologies (LP). Our cohort included subjects with none, mild, moderate, and severe LP caused by alcohol consumption. We noted a significant negative correlation of categorical data between liver steatosis and α-synuclein (αS) in the brain and a significant negative correlation between the extent of liver steatosis and fibrosis and the extent of αS in the brain. There was a significant negative association between the observation of Alzheimer’s type II astrocytes and αS pathology in the brain. No association was noted between LP and hyperphosphorylated τ (HPτ). No significant correlation could be seen between the extent of LP and the extent of HPτ, amyloid β protein (Aβ) or transactive DNA binding protein 43 (TDP43) in the brain. There were significant correlations observed between the extent of HPτ, Aβ, αS, and TDP43 in the brain and between liver steatosis, inflammation, and fibrosis. Subjects with severe LP displayed a higher frequency of Alzheimer’s type II astrocytes compared to those with no, or mild, LP. The assessed protein alterations were not more prevalent or severe in subjects with Alzheimer’s type II astrocytes in the brain. In all cases, dementia was attributed to a combination of altered proteins, i.e., mixed dementia and dementia was observed in 30% of those with mild LP when compared with 13% of those with severe LP. In summary, our results are in line with the outcome obtained by the two recent meta-analyses suggesting that subjects with a history of alcohol consumption seldom develop an α-synucleinopathy.

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来源期刊
Acta Neuropathologica
Acta Neuropathologica 医学-病理学
CiteScore
23.70
自引率
3.90%
发文量
118
审稿时长
4-8 weeks
期刊介绍: Acta Neuropathologica publishes top-quality papers on the pathology of neurological diseases and experimental studies on molecular and cellular mechanisms using in vitro and in vivo models, ideally validated by analysis of human tissues. The journal accepts Original Papers, Review Articles, Case Reports, and Scientific Correspondence (Letters). Manuscripts must adhere to ethical standards, including review by appropriate ethics committees for human studies and compliance with principles of laboratory animal care for animal experiments. Failure to comply may result in rejection of the manuscript, and authors are responsible for ensuring accuracy and adherence to these requirements.
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