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铝在神经和神经退行性疾病中的作用。

Aluminum in Neurological and Neurodegenerative Disease.

机构信息

Department of Physiology, University of Toronto, Toronto, ON, M5S 1A8, Canada.

Department of Neuropathology, Toronto General Hospital, Toronto, ON, M5G 2C4, Canada.

出版信息

Mol Neurobiol. 2019 Feb;56(2):1531-1538. doi: 10.1007/s12035-018-1441-x. Epub 2019 Jan 31.

Abstract

With continuing cooperation from 18 domestic and international brain banks over the last 36 years, we have analyzed the aluminum content of the temporal lobe neocortex of 511 high-quality human female brain samples from 16 diverse neurological and neurodegenerative disorders, including 2 groups of age-matched controls. Temporal lobes (Brodmann areas A20-A22) were selected for analysis because of their availability and their central role in massive information-processing operations including efferent-signal integration, cognition, and memory formation. We used the analytical technique of (i) Zeeman-type electrothermal atomic absorption spectrophotometry (ETAAS) combined with (ii) preliminary analysis from the advanced photon source (APS) hard X-ray beam (7 GeV) fluorescence raster-scanning (XRFR) spectroscopy device (undulator beam line 2-ID-E) at the Argonne National Laboratory, US Department of Energy, University of Chicago IL, USA. Neurological diseases examined were Alzheimer's disease (AD; N = 186), ataxia Friedreich's type (AFT; N = 6), amyotrophic lateral sclerosis (ALS; N = 16), autism spectrum disorder (ASD; N = 26), dialysis dementia syndrome (DDS; N = 27), Down's syndrome (DS; trisomy, 21; N = 24), Huntington's chorea (HC; N = 15), multiple infarct dementia (MID; N = 19), multiple sclerosis (MS; N = 23), Parkinson's disease (PD; N = 27), and prion disease (PrD; N = 11) that included bovine spongiform encephalopathy (BSE; "mad cow disease"), Creutzfeldt-Jakob disease (CJD) and Gerstmann-Straussler-Sheinker syndrome (GSS), progressive multifocal leukoencephalopathy (PML; N = 11), progressive supranuclear palsy (PSP; N = 24), schizophrenia (SCZ; N = 21), a young control group (YCG; N = 22; mean age, 10.2 ± 6.1 year), and an aged control group (ACG; N = 53; mean age, 71.4 ± 9.3 year). Using ETAAS, all measurements were performed in triplicate on each tissue sample. Among these 17 common neurological conditions, we found a statistically significant trend for aluminum to be increased only in AD, DS, and DDS compared to age- and gender-matched brains from the same anatomical region. This is the largest study of aluminum concentration in the brains of human neurological and neurodegenerative disease ever undertaken. The results continue to suggest that aluminum's association with AD, DDS, and DS brain tissues may contribute to the neuropathology of those neurological diseases but appear not to be a significant factor in other common disorders of the human brain and/or CNS.

摘要

在过去 36 年中,我们继续与 18 个国内外脑库合作,分析了 16 种不同神经退行性疾病的 511 个高质量女性人类大脑样本的颞叶新皮质的铝含量,其中包括 2 组年龄匹配的对照组。选择颞叶(布罗德曼区 A20-A22)进行分析,是因为它们的可用性以及它们在包括传出信号整合、认知和记忆形成在内的大量信息处理操作中的核心作用。我们使用了以下分析技术:(i)塞曼型电热原子吸收分光光度法(ETAAS)与(ii)美国能源部阿贡国家实验室、芝加哥大学伊利诺伊州、美国先进光子源(APS)硬 X 射线束(7 GeV)荧光光栅扫描(XRFR)光谱仪设备(波荡器光束线 2-ID-E)的初步分析相结合。研究的神经疾病包括阿尔茨海默病(AD;N=186)、弗里德里希共济失调型(AFT;N=6)、肌萎缩侧索硬化症(ALS;N=16)、自闭症谱系障碍(ASD;N=26)、透析性痴呆综合征(DDS;N=27)、唐氏综合征(DS;三体,21;N=24)、亨廷顿舞蹈病(HC;N=15)、多发性梗死性痴呆(MID;N=19)、多发性硬化症(MS;N=23)、帕金森病(PD;N=27)和朊病毒病(PrD;N=11),包括牛海绵状脑病(BSE;“疯牛病”)、克雅氏病(CJD)和格斯特曼-施特劳斯勒-谢因克综合征(GSS)、进行性多灶性白质脑病(PML;N=11)、进行性核上性麻痹(PSP;N=24)、精神分裂症(SCZ;N=21)、年轻对照组(YCG;N=22;平均年龄为 10.2±6.1 岁)和老年对照组(ACG;N=53;平均年龄为 71.4±9.3 岁)。使用 ETAAS,对每个组织样本进行了三次重复测量。在这 17 种常见神经疾病中,我们发现,与同一解剖区域的年龄和性别匹配的大脑相比,铝在 AD、DS 和 DDS 中呈统计学显著增加趋势。这是对人类神经退行性疾病大脑中铝浓度进行的最大规模研究。结果继续表明,铝与 AD、DDS 和 DS 脑组织的关联可能导致这些神经疾病的神经病理学,但似乎不是人类大脑和/或中枢神经系统其他常见疾病的重要因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b87/6402994/d99d09876d2b/nihms-1520423-f0001.jpg

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