Pan Feng-Feng, Huang Qi, Wang Ying, Wang Yi-Fan, Guan Yi-Hui, Xie Fang, Guo Qi-Hao
Department of Gerontology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
PET Center, Huashan Hospital, Fudan University, Shanghai, China.
Front Aging Neurosci. 2022 Mar 23;14:832700. doi: 10.3389/fnagi.2022.832700. eCollection 2022.
Plasma amyloid-β (Aβ) was associated with brain Aβ deposition and Alzheimer's disease (AD) development. However, changes of plasma Aβ over the course of cognitive decline in the Alzheimer's continuum remained uncertain. We recruited 449 participants to this study, including normal controls (NC), subjective cognitive decline (SCD), mild cognitive impairment (MCI), AD, and non-AD dementia. All the participants underwent plasma Aβ42, Aβ40, and t-tau measurements with single-molecule array (Simoa) immunoassay and PET scan with 18F-florbetapir amyloid tracer. In the subgroup of Aβ-PET positive, plasma Aβ42 and Aβ42/Aβ40 ratio was significantly lower in AD than NC, SCD and MCI, yet SCD had significantly higher levels of plasma Aβ42 than both NC and MCI. In the diagnostic groups of MCI and dementia, participants with Aβ-PET positive had lower plasma Aβ42 and Aβ42/40 ratio than participants with Aβ-PET negative, and the increasing levels of plasma Aβ42 and Aβ42/40 ratio indicated lower risks of Aβ-PET positive. However, in the participants with SCD, plasma Aβ42 and Aβ40 were higher in the subgroup of Aβ-PET positive than Aβ-PET negative, and the increasing levels of plasma Aβ42 and Aβ40 indicated higher risks of Aβ-PET positive. No significant association was observed between plasma Aβ and Aβ-PET status in normal controls. These findings showed that, in the continuum of AD, plasma Aβ42 had a significantly increasing trend from NC to SCD before decreasing in MCI and AD. Furthermore, the predictive values of plasma Aβ for brain amyloid deposition were inconsistent over the course of cognitive decline.
血浆淀粉样β蛋白（Aβ）与脑Aβ沉积及阿尔茨海默病（AD）的发展相关。然而，在阿尔茨海默病连续体认知衰退过程中血浆Aβ的变化仍不明确。我们招募了449名参与者进行本研究，包括正常对照（NC）、主观认知衰退（SCD）、轻度认知障碍（MCI）、AD以及非AD痴呆患者。所有参与者均采用单分子阵列（Simoa）免疫分析法进行血浆Aβ42、Aβ40和总tau（t-tau）检测，并使用18F-氟代贝他吡淀粉样示踪剂进行PET扫描。在Aβ-PET阳性亚组中，AD患者的血浆Aβ42和Aβ42/Aβ40比值显著低于NC、SCD和MCI患者，但SCD患者的血浆Aβ42水平显著高于NC和MCI患者。在MCI和痴呆的诊断组中，Aβ-PET阳性的参与者血浆Aβ42和Aβ42/40比值低于Aβ-PET阴性的参与者，血浆Aβ42和Aβ42/40比值升高表明Aβ-PET阳性风险较低。然而，在SCD参与者中，Aβ-PET阳性亚组的血浆Aβ42和Aβ40高于Aβ-PET阴性亚组，血浆Aβ42和Aβ40升高表明Aβ-PET阳性风险较高。在正常对照中，未观察到血浆Aβ与Aβ-PET状态之间存在显著关联。这些发现表明，在AD连续体中，血浆Aβ42从NC到SCD呈显著上升趋势，然后在MCI和AD中下降。此外，在认知衰退过程中，血浆Aβ对脑淀粉样沉积的预测价值并不一致。
