JAMA Neurology:阿尔茨海默病患者8种血浆淀粉样蛋白Aβ42/40检测方法的比较

2021-11-15 Naomi MedSci原创

检测阿尔茨海默病(AD)中淀粉样蛋白(Aβ)病理是生物标记物在临床治疗中实施的一个重大进步。某些基于高精度免疫沉淀-耦合质谱法的方法在检测脑Aβ病理时比大多数血浆Aβ42/40免疫分析方法表现更得更好

      检测阿尔茨海默病(AD)中淀粉样蛋白(Aβ)病理的LOOD测试将是生物标记物在临床治疗中实施的一个重大进步,并在药物试验中非常有用。血液中Aβ的可靠测量被证明是具有挑战性的,直到先进的质谱和免疫检测方法的发展。在2016年,用超灵敏的SIMOA免疫测定法评估的血浆Aβ42/40被证明能以中等准确度检测异常的脑脊液β或β正电子发射断层扫描。高精度免疫沉淀-耦合质谱法(IP-MS)测定的血浆Aβ42/40后来被报道与β-PET相关,并与高精度的脑Aβ负荷异常或将来转为β-PET阳性的高风险个体相鉴别。不同的Aβ分析和平台在整个研究中的不同表现可能部分是由于队列特征(例如,样本大小、纳入的诊断组和结果测量)和分析前样本处理的差异。为了最大限度地减少这些偏倚,近日有研究人员对瑞典BIOFINDER研究中的同一组早期AD患者进行了8种Aβ检测方法的一一比较,以评估了不同方法测定的血浆Aβ42/40与正常脑脊液Aβ42/40或Aβ-PET状态的鉴别能力。

      这项研究包括182 BIOFINDER队列中认知正常的参与者和104名轻度认知障碍的患者,他们在瑞典3家不同的医院登记,从2010年到2014年接受了β正电子发射断层扫描、脑脊液和血浆采集

      采用华盛顿大学开发的免疫沉淀耦合质谱法(IP-MS-WASU)、Araclon公司开发的无抗体液相色谱质谱(LC-MS-ARC)和罗氏诊断公司(IA-ELC)、欧洲免疫学公司(IA-EI)、阿姆斯特丹大学医学中心、ADX神经科学公司和Quanterix公司的免疫分析法(IA-N4PE)测定血浆Aβ42/40。用岛津的IP-MS法(IP-MS-SHIM)和哥德堡大学的IP-MS-UGOT法(IP-MS-UGOT)和Quanterix公司的免疫测定法(IA-Quan)分别测定了2 0 0名受试者的血浆Aβ42/40。

      为了验证,来自阿尔茨海默病神经成像计划的12名参与者(51名认知正常,51名轻度认知障碍,20名AD痴呆)接受了Aβ-PET和血浆Aβ评估,使用IP-MS-WASU,IP-MS-SHIM,IP-MS-UGOT,IA-ELC,IA-N4PE和IA-Quan分析。

      8种不同方法定量检测血浆A-β42/40对异常脑脊液A-β42/40和A-β-PET42/40状态的判别准确性

  • 共有408名参与者参与了这项研究。
  • 在BioFINDER队列中,平均年龄(SD)为71.6(5.6)岁,其中49.3%为女性。
  • 血浆IP-MS-WASU Aβ42/40与LC-MS-Arc Aβ42/40、IA-EI Aβ42/40和IA-N4PE Aβ42/40的准确性(受试者工作特征曲线下面积分别为0.86和0.81~0.90)相比,差异有统计学意义(P<0.05)。
  • 血浆IP-MS-WASU Aβ42/40显著优于IP-MS-UGOT Aβ42/40和IA-QUAβ42/40(AUC0.84vs0.68和0.64;P<0.001),而IP-MS-WASU Aβ42/40和IP-MS-Shim Aβ42/40的AUC无明显差异(0.87vs0.83;P=0.16)。
  • 当使用Aβ-PET作为结果时,结果是相似的。
  • 血浆IPMS-WASU Aβ42/40和IPMS-Shim Aβ42/40与脑脊液Aβ42/40的相关系数最高(r=0.56~0.65)。
  • BioFINDER的结果在阿尔茨海默病神经成像倡议队列(平均[SD]年龄,72.4[5.4]岁;43.4%的女性)中得到了复制,其中IP-MS-WASU检测的表现明显优于IP-MS-UGOT、IA-ELC、IA-N4PE和IA-Quan检测,但IP-MS-Shim检测没有。

两个独立队列的结果表明,某些基于MS的方法在检测脑Aβ病理时比大多数血浆Aβ42/40免疫分析方法表现得更好。

文献来源:https://jamanetwork-com.washington.80599.net/journals/jamaneurology/fullarticle/2784411

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    2022-09-26 feifers
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    2022-02-01 yinhl1978
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    2021-11-16 膀胱癌

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在这篇文章中,作者提供了基于生物标志物的AD分期系统的最新综述,并考虑了基于液体生物标志物的未来分期系统。

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iMEP技术还能够熟练量化与疾病发病机制相关的不同外泌体生物标志物水平。

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该研究表明,听力损失加重了AD野生型小鼠和小鼠模型的认知障碍。

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