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阿尔茨海默病患者外周转运蛋白与血浆淀粉样蛋白-β的关系与认知正常对照不同:倾向评分匹配分析。

Relationship Between Peripheral Transport Proteins and Plasma Amyloid-β in Patients with Alzheimer's Disease Were Different from Cognitively Normal Controls: A Propensity Score Matching Analysis.

机构信息

Department of Neurology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Huxian Hospital of Traditional Chinese Medicine, Xi'an, China.

出版信息

J Alzheimers Dis. 2020;78(2):699-709. doi: 10.3233/JAD-191320.

Abstract

BACKGROUND

Transport proteins, soluble LRP1 (sLRP1) and soluble RAGE (sRAGE), play a pivotal role in the peripheral clearance of plasma amyloid-β (Aβ). However, their relationship is seldom discussed, especially in Alzheimer's disease (AD).

OBJECTIVE

To explore whether their relationship in patients with AD varied from those in cognitively normal (CN) controls.

METHODS

We initially recruited 70 patients with AD and 725 CN controls, then applied propensity score matching (PSM) analysis to balance the differences between two groups. Plasma levels of sLRP1, sRAGE, and Aβ were measured using commercial ELISA kits and log transformed when skewed distributed. The relationship between sLRP1/sRAGE and plasma Aβ were analyzed using Pearson's correlation analysis followed by multiple linear regression separately in the original population and matched participants.

RESULTS

After PSM, 70 patients with AD and 140 matched controls were included for further analysis. Log sLRP1 was positively correlated with plasma Aβ40 in matched CN controls (r = 0.222, p = 0.008) but not in patients with AD (r = 0.137, p = 0.260). After multivariable adjustment, Log sLRP1 remained significantly associated with plasma Aβ40 in the CN group (β= 7.347, p = 0.014) but not in the AD group (β= 10.409, p = 0.105). In contrast, Log sLRP1 was not correlated with plasma Aβ42 in patients with AD or CN controls, and Log sRAGE was consistently not associated with plasma Aβ40 or Aβ42 in either group.

CONCLUSION

The significant correlation between sLRP1 and plasma Aβ40 present in CN controls was not found in patients with AD, suggesting that their relationship was different in AD. However, the specific mechanisms and its influence on cerebral amyloid burden require further validation.

摘要

背景

转运蛋白可溶性低密度脂蛋白受体相关蛋白 1(sLRP1)和可溶性晚期糖基化终末产物受体(sRAGE)在血浆淀粉样β(Aβ)的外周清除中发挥关键作用。然而,它们之间的关系很少被讨论,特别是在阿尔茨海默病(AD)中。

目的

探讨 AD 患者与认知正常(CN)对照组之间 sLRP1 和 sRAGE 之间的关系是否存在差异。

方法

我们最初招募了 70 名 AD 患者和 725 名 CN 对照组,然后应用倾向评分匹配(PSM)分析来平衡两组之间的差异。使用商业 ELISA 试剂盒测量血浆 sLRP1、sRAGE 和 Aβ 水平,当分布偏态时进行对数转换。在原始人群和匹配参与者中,分别使用 Pearson 相关分析和多元线性回归分析 sLRP1/sRAGE 与血浆 Aβ 之间的关系。

结果

PSM 后,纳入 70 名 AD 患者和 140 名匹配对照组进行进一步分析。匹配的 CN 对照组中,Log sLRP1 与血浆 Aβ40 呈正相关(r=0.222,p=0.008),但在 AD 患者中无相关性(r=0.137,p=0.260)。在多变量调整后,Log sLRP1 与 CN 组血浆 Aβ40 仍显著相关(β=7.347,p=0.014),但与 AD 组无相关性(β=10.409,p=0.105)。相反,Log sLRP1 与 AD 患者或 CN 对照组的血浆 Aβ42 不相关,Log sRAGE 与两组的血浆 Aβ40 或 Aβ42 均不相关。

结论

CN 对照组中 sLRP1 与血浆 Aβ40 之间的显著相关性在 AD 患者中未发现,提示它们之间的关系在 AD 中不同。然而,其具体机制及其对脑淀粉样负荷的影响需要进一步验证。

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