Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China.
National Center for Neurological Diseases in China, Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, 12Th Wulumuqi Zhong Road, Shanghai, 200040, China.
Alzheimers Res Ther. 2023 Apr 1;15(1):69. doi: 10.1186/s13195-023-01217-6.
Previous studies have suggested a correlation between elevated levels of β-microglobulin (B2M) and cognitive impairment. However, the existing evidence is insufficient to establish a conclusive relationship. This study aims to analyze the link of plasma B2M to cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers and cognition.
To track the dynamics of plasma B2M in preclinical AD, 846 cognitively healthy individuals in the Chinese Alzheimer's Biomarker and LifestylE (CABLE) cohort were divided into four groups (suspected non-AD pathology [SNAP], 2, 1, 0) according to the NIA-AA criteria. Multiple linear regression models were employed to examine the plasma B2M's relationship with cognitive and CSF AD biomarkers. Causal mediation analysis was conducted through 10,000 bootstrapped iterations to explore the mediating effect of AD pathology on cognition.
We found that the levels of plasma B2M were increased in stages 1 (P = 0.0007) and 2 (P < 0.0001), in contrast to stage 0. In total participants, higher levels of B2M were associated with worse cognitive performance (P = 0.006 for MMSE; P = 0.012 for MoCA). Moreover, a higher level of B2M was associated with decreases in Aβ (P < 0.001) and Aβ/Aβ (P = 0.015) as well as increases in T-tau/Aβ (P < 0.001) and P-tau/Aβ (P < 0.001). The subgroup analysis found B2M correlated with Aβ in non-APOE ε4 individuals (P < 0.001) but not in APOE ε4 carriers. Additionally, the link between B2M and cognition was partially mediated by Aβ pathology (percentage: 8.6 to 19.3%), whereas tau pathology did not mediate this effect.
This study demonstrated the association of plasma B2M with CSF AD biomarkers as well as a possible important role of Aβ pathology in the association between B2M and cognitive impairment, particularly in cognitively normal individuals. The results indicated that B2M could be a potential biomarker for preclinical AD and might have varied functions throughout various stages of preclinical AD progression.
先前的研究表明β-微球蛋白（B2M）水平升高与认知障碍有关。然而，现有证据尚不足以确定两者之间的因果关系。本研究旨在分析血浆 B2M 与脑脊液（CSF）阿尔茨海默病（AD）生物标志物和认知之间的关联。
为了跟踪临床前 AD 中血浆 B2M 的动态变化，根据 NIA-AA 标准，将中国阿尔茨海默病生物标志物和生活方式（CABLE）队列中的 846 名认知健康个体分为四组（疑似非 AD 病理组 [SNAP]、2 组、1 组、0 组）。采用多元线性回归模型来检验血浆 B2M 与认知和 CSF AD 生物标志物之间的关系。通过 10000 次自举迭代进行因果中介分析，以探讨 AD 病理对认知的中介作用。
我们发现，与 0 期相比，1 期（P=0.0007）和 2 期（P<0.0001）患者的血浆 B2M 水平升高。在所有参与者中，较高的 B2M 水平与较差的认知表现相关（MMSE：P=0.006；MoCA：P=0.012）。此外，较高的 B2M 水平与 Aβ 降低相关（P<0.001）和 Aβ/Aβ 降低（P=0.015），以及 T-tau/Aβ 升高（P<0.001）和 P-tau/Aβ 升高（P<0.001）相关。亚组分析发现，在非 APOE ε4 个体中，B2M 与 Aβ 相关（P<0.001），但在 APOE ε4 携带者中则不然。此外，B2M 与认知之间的关联部分通过 Aβ 病理介导（比例：8.6% 至 19.3%），而 tau 病理则没有介导该效应。
本研究表明，血浆 B2M 与 CSF AD 生物标志物相关，Aβ 病理可能在 B2M 与认知障碍之间的关联中起重要作用，尤其是在认知正常个体中。结果表明，B2M 可能是临床前 AD 的潜在生物标志物，并且在临床前 AD 进展的不同阶段可能具有不同的功能。
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