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Cerebrospinal fluid proteomics and biological heterogeneity in Alzheimer's disease: A literature review.
Critical Reviews in Clinical Laboratory Sciences ( IF 10.0 ) Pub Date : 2019-11-07 , DOI: 10.1080/10408363.2019.1670613 Kirsten E J Wesenhagen 1 , Charlotte E Teunissen 2 , Pieter Jelle Visser 1 , Betty M Tijms 1
Critical Reviews in Clinical Laboratory Sciences ( IF 10.0 ) Pub Date : 2019-11-07 , DOI: 10.1080/10408363.2019.1670613 Kirsten E J Wesenhagen 1 , Charlotte E Teunissen 2 , Pieter Jelle Visser 1 , Betty M Tijms 1
Affiliation
Alzheimer's disease (AD) is the most common cause of dementia and is characterized by aggregation of amyloid and tau proteins in the brain. Results from genetic studies suggest that the pathophysiology underlying AD is complex, but studying this complexity in patients remains difficult. The cerebrospinal fluid (CSF) proteome contains a large number of proteins that can reflect ongoing biological processes. Proteomics techniques can be used to measure many proteins simultaneously in individual patients and may therefore provide an opportunity to study AD disease mechanisms. Here, we review the CSF proteomics literature to identify proteins consistently associated with AD, and perform pathway analyses on these proteins to study which biological processes may be involved in the disease.We performed a literature search of studies that investigated CSF proteomic alterations related to AD. We included original research articles when they measured at least 10 proteins in (antemortem) CSF in at least 10 individuals with AD, mild cognitive impairment (MCI) or controls. We examined if proteins were consistently related to AD, defined as consistent increase or decrease in AD vs. controls across studies. Next, we used the proteins identified as input to pathway analyses using Reactome to investigate which biological processes were enriched.In total, 29 studies were included that investigated AD-related changes to the CSF proteome, including a total of 1434 individuals with AD (of whom 47.1% had a CSF biomarker profile and 9.6% a postmortem examination consistent with AD) and 1380 controls. The studies reported 1 to 138 proteins associated with AD, of which 97 proteins were reported by two or more studies. Among proteins that were measured in more than one study, 27 (27.8%) showed consistent increases, 15 (15.5%) consistent decreases and 55 (56.7%) had contrasting results. Pathway analyses showed that AD-related proteins were enriched for hemostasis, lipoprotein and extracellular matrix pathways.These results indicate that proteomic alterations in CSF associated with AD reflect involvement of various biological pathways. The frequent occurrence of inconsistent protein level changes reported by different studies suggests that additional biological and/or (pre)analytical factors may influence the CSF proteome in AD, which should be further investigated in order to improve understanding of the biological complexity underlying AD.
中文翻译:
脑脊髓液蛋白质组学和阿尔茨海默氏病的生物学异质性:文献综述。
阿尔茨海默氏病(AD)是痴呆症最常见的病因,其特征是大脑中淀粉样蛋白和tau蛋白的聚集。遗传研究的结果表明,AD的病理生理学很复杂,但是在患者中研究这种复杂性仍然很困难。脑脊液(CSF)蛋白质组包含大量蛋白质,可以反映正在进行的生物学过程。蛋白质组学技术可用于同时测量单个患者中的许多蛋白质,因此可能提供研究AD疾病机制的机会。在这里,我们回顾了CSF蛋白质组学文献,以鉴定与AD一致的蛋白质,并对这些蛋白质进行途径分析,以研究该疾病可能涉及的生物学过程。我们对研究与AD相关的CSF蛋白质组学改变的研究进行了文献检索。当他们在至少10名患有AD,轻度认知障碍(MCI)或对照的个体中测量(死前)CSF中的至少10种蛋白质时,我们纳入了原始研究文章。我们检查了蛋白质是否始终与AD相关,定义为整个研究中AD与对照的一致增加或减少。接下来,我们使用鉴定出的蛋白质作为使用Reactome进行途径分析的输入,以研究哪些生物学过程得到了丰富。总共包括29项研究,研究了与AD相关的CSF蛋白质组变化,包括总共1434例患有AD(他们中有47.1%的人具有CSF生物标志物特征,而死后检查的9.6%与AD相符)和1380例对照。这些研究报告了1至138种与AD相关的蛋白质,其中两项或更多研究报告了97种蛋白质。在一项以上研究中测量的蛋白质中,有27种(27.8%)呈持续增加趋势,有15种(15.5%)呈持续下降趋势,有55种(56.7%)呈对比结果。通路分析表明,AD相关蛋白富含止血,脂蛋白和细胞外基质通路,这些结果表明与AD相关的CSF蛋白质组学改变反映了多种生物学通路的参与。不同研究报告的蛋白质水平变化不一致的情况经常发生,这表明其他生物学和/或(分析前)因素可能会影响AD中的CSF蛋白质组,应对此进行进一步研究,以增进对AD背后的生物学复杂性的了解。
更新日期:2020-04-20
中文翻译:
脑脊髓液蛋白质组学和阿尔茨海默氏病的生物学异质性:文献综述。
阿尔茨海默氏病(AD)是痴呆症最常见的病因,其特征是大脑中淀粉样蛋白和tau蛋白的聚集。遗传研究的结果表明,AD的病理生理学很复杂,但是在患者中研究这种复杂性仍然很困难。脑脊液(CSF)蛋白质组包含大量蛋白质,可以反映正在进行的生物学过程。蛋白质组学技术可用于同时测量单个患者中的许多蛋白质,因此可能提供研究AD疾病机制的机会。在这里,我们回顾了CSF蛋白质组学文献,以鉴定与AD一致的蛋白质,并对这些蛋白质进行途径分析,以研究该疾病可能涉及的生物学过程。我们对研究与AD相关的CSF蛋白质组学改变的研究进行了文献检索。当他们在至少10名患有AD,轻度认知障碍(MCI)或对照的个体中测量(死前)CSF中的至少10种蛋白质时,我们纳入了原始研究文章。我们检查了蛋白质是否始终与AD相关,定义为整个研究中AD与对照的一致增加或减少。接下来,我们使用鉴定出的蛋白质作为使用Reactome进行途径分析的输入,以研究哪些生物学过程得到了丰富。总共包括29项研究,研究了与AD相关的CSF蛋白质组变化,包括总共1434例患有AD(他们中有47.1%的人具有CSF生物标志物特征,而死后检查的9.6%与AD相符)和1380例对照。这些研究报告了1至138种与AD相关的蛋白质,其中两项或更多研究报告了97种蛋白质。在一项以上研究中测量的蛋白质中,有27种(27.8%)呈持续增加趋势,有15种(15.5%)呈持续下降趋势,有55种(56.7%)呈对比结果。通路分析表明,AD相关蛋白富含止血,脂蛋白和细胞外基质通路,这些结果表明与AD相关的CSF蛋白质组学改变反映了多种生物学通路的参与。不同研究报告的蛋白质水平变化不一致的情况经常发生,这表明其他生物学和/或(分析前)因素可能会影响AD中的CSF蛋白质组,应对此进行进一步研究,以增进对AD背后的生物学复杂性的了解。