Can plasma amyloid‐beta levels be considered as a potential biomarker to discriminate preclinical Alzheimer’s disease?

Abstract Background We investigated plasma amyloid‐beta (Aβ) levels across Alzheimer’s spectrum from normal control (NC) to cognitive impairment (CI) vis preclinical AD (PreAD) as well as their association with central biomarkers to explore their potential as a pre‐screening tool for identifying early AD. Method One hundred and thirty‐nine participants (50 NC, 34 PreAD and 55 CI) from SILCODE project and memory clinic in Xuanwu Hospital were included. Preclinical AD patients were defined as cognitively normal subjects with positive amyloid‐PET. Cognitive impairment patients were defined as objective cognitive impairment due to AD. Plasma Aβ40 and Aβ42 were measured using Meso Scale Discovery technology. Analysis of covariance (ANCOVA) was used to examine the plasma Aβ levels across the three groups. A general linear model analysis was used to test for association between plasma Aβ levels and amyloid burden, gray matter volume (GM) and amplitude of low frequency fluctuation (ALFF). Further, mediating effect of amyloid burden on association between plasma Aβ levels and neurodegeneration biomarkers were tested. Result The levels of plasma Aβ42/Aβ40 and Aβ42 levels were different among three groups (for Aβ42 [pg/ml]: 12.27(4.35) in NC, 10.93(3.00) in PreAD, and 10.08(2.73) in CI [P=.045 adjusted for carrier of ApoE ε4 allele, age, sex, and education]; for Aβ42/Aβ40: 0.017(0.005) in NC, 0.014(0.003) in PreAD, and 0.013(0.004) in CI [P <. 001]) (Figure 1). Globally, Plasma Aβ42 and Aβ42/Aβ40 ratio negatively correlated with global SUVR (p=0.007 and p=0.001) and positively correlated with gray matter volume (p=0.011 and p<0.001). Plasma Aβ40 showed significantly positive correlation with ALFF (p=0.008) and Aβ42/Aβ40 ratio showed an opposite correlation with ALFF (p=0.019) (Figure 2). Global SUVR significantly mediates the relationship between plasma Aβ42/Aβ40 ratio and gray matter volume (average causal mediation effects 95%CI: 13.912‐86.439). Conclusion The present data show plasma Aβ42/Aβ40 ratio were lower in patients with cognitive impairment than preclinical AD than normal controls. Plasma Aβ were correlated with brain amyloid deposition, structural atrophy and functional alteration. These results suggest the potential for plasma Aβ serving as a more cost‐effective prescreening tool in clinical practice.