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阿尔茨海默病脑内报道的蛋白质变化汇编。

Compilation of reported protein changes in the brain in Alzheimer's disease.

机构信息

Biomedical Hosting LLC, Arlington, MA, 02140, USA.

Brain and Mind Centre and School of Medical Sciences, University of Sydney, Camperdown, NSW, 2050, Australia.

出版信息

Nat Commun. 2023 Jul 25;14(1):4466. doi: 10.1038/s41467-023-40208-x.

Abstract

Proteomic studies of human Alzheimer's disease brain tissue have potential to identify protein changes that drive disease, and to identify new drug targets. Here, we analyse 38 published Alzheimer's disease proteomic studies, generating a map of protein changes in human brain tissue across thirteen brain regions, three disease stages (preclinical Alzheimer's disease, mild cognitive impairment, advanced Alzheimer's disease), and proteins enriched in amyloid plaques, neurofibrillary tangles, and cerebral amyloid angiopathy. Our dataset is compiled into a searchable database (NeuroPro). We found 848 proteins were consistently altered in 5 or more studies. Comparison of protein changes in early-stage and advanced Alzheimer's disease revealed proteins associated with synapse, vesicle, and lysosomal pathways show change early in disease, but widespread changes in mitochondrial associated protein expression change are only seen in advanced Alzheimer's disease. Protein changes were similar for brain regions considered vulnerable and regions considered resistant. This resource provides insight into Alzheimer's disease brain protein changes and highlights proteins of interest for further study.

摘要

人类阿尔茨海默病脑组织的蛋白质组学研究有潜力识别驱动疾病的蛋白质变化,并确定新的药物靶点。在这里,我们分析了 38 项已发表的阿尔茨海默病蛋白质组学研究,生成了人类脑组织中 13 个脑区、3 个疾病阶段(临床前阿尔茨海默病、轻度认知障碍、晚期阿尔茨海默病)和富含淀粉样斑块、神经原纤维缠结和脑淀粉样血管病的蛋白质变化图谱。我们的数据集被汇编成一个可搜索的数据库(NeuroPro)。我们发现 848 种蛋白质在 5 种或更多研究中一致改变。早期和晚期阿尔茨海默病的蛋白质变化比较表明,与突触、囊泡和溶酶体途径相关的蛋白质在疾病早期发生变化,但只有在晚期阿尔茨海默病中才会观察到与线粒体相关的蛋白质表达变化的广泛变化。被认为易受影响的脑区和被认为具有抗性的脑区的蛋白质变化相似。该资源提供了对阿尔茨海默病大脑蛋白质变化的深入了解,并突出了进一步研究的有趣蛋白质。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/563d/10368642/5017208fded7/41467_2023_40208_Fig1_HTML.jpg

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