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阿尔茨海默病中Aβ的动态血药浓度及Aβ情况

Dynamic Blood Concentrations of Aβ and Aβ in Alzheimer's Disease.

作者信息

Yang Yuan-Han, Huang Ling-Chun, Hsieh Sun-Wung, Huang Li-Ju

机构信息

Department of Neurology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.

Department of Neurology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.

出版信息

Front Cell Dev Biol. 2020 Aug 11;8:768. doi: 10.3389/fcell.2020.00768. eCollection 2020.

Abstract

Amyloid-beta (Aβ) is produced by the cleavage of amyloid precursor proteins in the cell membrane by β-secretase and γ-secretase into a monomeric form with peptides of different lengths such as Aβ or Aβ, which is then transformed into oligomeric and fibril forms and is considered to be one of the hallmarks of Alzheimer's disease (AD). The plasma concentrations of Aβ and Aβ are unstable after blood samples have been obtained. In order to examine the dynamic changes of plasma Aβ and Aβ in blood samples, we used fresh blood samples in ethylenediaminetetraacetic acid tubes from 32 clinically diagnosed AD patients. Each sample was subdivided into eight sub-samples, and levels of Aβ and Aβ were measured at 0 (baseline), 0.5, 1, 2, 3, 5, 8, and 24 h, respectively. All samples were incubated at 37°C before being measuring. The results showed that compared to baseline, 87.5 and 62.5% of the patients had higher plasma levels of Aβ and Aβ at 24 h, respectively. The patients with an increased amyloid level did not have a significantly different apo-lipoprotein E4 allele (APOE4) gene status for either Aβ ( = 0.422) or Aβ ( = 1.000). However, for plasma Aβ, the APOE4 carriers had a significantly lower level than the non-carriers at baseline [31.2 ± 6.5 (mean ± SD) ng/ml vs. 50.4 ± 47.7 ng/ml, = 0.031] and 0.5 h (37.5 ± 7.6 ng/ml vs. 51.9 ± 30.8 ng/ml, = 0.043). There were no significant differences between the APOE4 carriers and non-carriers in plasma Aβ concentration at 1, 2, 3, 5, 8, and 24 h ( = 0.112, = 0.086, = 0.112, = 0.263, = 0.170 and = 0.621, respectively). The Aβ level was related to disease severity as assessed using the clinical dementia rating (CDR) scale. Patients with advanced stages of dementia (CDR = 1 and CDR = 2) had a significantly higher Aβ level compared to those with very mild stage dementia (CDR = 0.5) at all time points ( < 0.05) except for 24 h ( = 0.059). Our findings illustrate the effects of APOE4 status on dynamic changes in plasma Aβ and Aβ levels, and significant associations between Aβ level and disease severity. Further studies are needed to investigate the exact mechanisms of how APOE4 affects the dynamic changes in plasma Aβ and Aβ, and the association between Aβ and advanced dementia.

摘要

β淀粉样蛋白(Aβ)由细胞膜中的淀粉样前体蛋白经β-分泌酶和γ-分泌酶切割产生,形成不同长度肽段的单体形式,如Aβ或Aβ,随后转变为寡聚体和纤维状形式,被认为是阿尔茨海默病(AD)的标志性特征之一。采集血样后,血浆中Aβ和Aβ的浓度不稳定。为了检测血样中血浆Aβ和Aβ的动态变化,我们使用了来自32例临床诊断为AD患者的乙二胺四乙酸管中的新鲜血样。每个样本被细分为8个亚样本,分别在0(基线)、0.5、1、2、3、5、8和24小时测量Aβ和Aβ的水平。所有样本在测量前于37℃孵育。结果显示,与基线相比,分别有87.5%和62.5%的患者在24小时时血浆Aβ和Aβ水平升高。淀粉样蛋白水平升高的患者,其载脂蛋白E4等位基因(APOE4)状态在Aβ(=0.422)或Aβ(=1.000)方面没有显著差异。然而,对于血浆Aβ,APOE4携带者在基线时[31.2±6.5(平均值±标准差)ng/ml对50.4±47.7 ng/ml,=0.031]和0.5小时时(37.5±7.6 ng/ml对51.9±30.8 ng/ml,=0.043)的水平显著低于非携带者。在1、2、3、5、8和24小时时,APOE4携带者和非携带者的血浆Aβ浓度没有显著差异(分别为=0.112、=0.086、=0.112、=0.263、=0.170和=0.621)。Aβ水平与使用临床痴呆评定(CDR)量表评估的疾病严重程度相关。除24小时(=0.059)外,在所有时间点,痴呆晚期(CDR=1和CDR=2)的患者与极轻度痴呆(CDR=0.5)的患者相比,Aβ水平显著更高(<0.05)。我们的研究结果说明了APOE4状态对血浆Aβ和Aβ水平动态变化的影响,以及Aβ水平与疾病严重程度之间的显著关联。需要进一步研究来探讨APOE4影响血浆Aβ和Aβ动态变化的确切机制,以及Aβ与晚期痴呆之间的关联。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/307d/7432270/b0cf6696e138/fcell-08-00768-g001.jpg

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