Plasma β2-microglobulin and cerebrospinal fluid biomarkers of Alzheimer's disease pathology in cognitively intact older adults: the CABLE study

Background Previous studies have suggested a correlation between elevated levels of beta(2)-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. Methods 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. Results 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 A beta(1-42) (P < 0.001) and A beta(1-42)/A beta(1-40) (P = 0.015) as well as increases in T-tau/A beta(1-42) (P < 0.001) and P-tau/A beta(1-42) (P < 0.001). The subgroup analysis found B2M correlated with A beta(1-42) in non-APOE epsilon 4 individuals (P < 0.001) but not in APOE epsilon 4 carriers. Additionally, the link between B2M and cognition was partially mediated by A beta pathology (percentage: 8.6 to 19.3%), whereas tau pathology did not mediate this effect. Conclusions This study demonstrated the association of plasma B2M with CSF AD biomarkers as well as a possible important role of A beta 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.

Automated summary

This study analyzed the link between plasma B2M and CSF AD biomarkers as well as cognition. The results showed that B2M levels were associated with cognitive impairment and changes in AD biomarkers. This suggests that B2M could be a potential biomarker for preclinical AD.