Plasma amyloid‐β, total tau, and neurofilament light chain across the Alzheimer clinical spectrum: a population‐based study

Abstract

AbstractBackgroundPlasma biomarkers have emerged as a promising approach for defining mild cognitive impairment (MCI) and Alzheimer’s disease (AD). We aimed to characterize Alzheimer’s plasma biomarkers across the clinical continuum of AD, and to assess their ability to differentiate between MCI, AD, and normal cognition.MethodThis population‐based study engaged 1446 rural‐dwelling older adults (age≥60 years, 61.0% women) derived from Multimodal Interventions to Delay Dementia and Disability in Rural China study; of these, 902 were defined with normal cognition, 402 with MCI, and 142 with AD according to the international criteria. Plasma amyloid‐beta (Aβ), total‐tau (t‐tau), and neurofilament light chain (NfL) concentrations were analysed using Simoa platform. Data were analysed using the logistic and general linear models, and receiver operating characteristic (ROC) analysis.ResultPlasma concentrations of Aβ40, Aβ42, t‐tau, and NfL were significantly increased with age (P<0.01). Women had higher plasma Aβ2 (age‐adjusted β = 0.62; 95%CI = 0.30‐0.94), Aβ42/Aβ40 ratio (0.19; 0.01‐0.36) and lower NfL concentrations (‐0.11; ‐0.16‐ ‐0.06). Plasma Aβ42 (age‐ and sex‐adjusted β = ‐0.73; ‐1.15‐ ‐0.31) and Aβ42/Aβ40 ratio (‐0.51; ‐0.74‐ ‐0.29) were lower in APOE ε4 carriers than that in non‐carriers. Plasma Aβ40 and Aβ42/Aβ40 ratio showed an increased and decreased trend, respectively, across AD clinical spectrum. Plasma t‐tau and t‐tau/Aβ42 ratio were higher in people with AD than those with MCI or normal cognition. Plasma NfL was increased across the AD clinical continuum and outperformed other Alzheimer’s biomarkers in differentiating AD from normal cognition (area under the ROC curve [AUC] = 0.75). However, all of these plasma biomarkers performed poorly to distinguish MCI from normal cognition (AUC<0.60). When adding plasma NfL to the basic model that included age, sex, education, and APOE genotype, the AUC was 0.87 for differentiating between AD and normal cognition, 0.79 between AD and MCI, and 0.64 between MCI and normal cognition.ConclusionAge, sex, and APOE genotype should be considered in clinical interpretation of Alzheimer’s plasma biomarkers. Plasma Aβ, t‐tau, and NfL concentrations differ across the cognitive continuum, but plasma NfL, which starts to elevate in the early stages of AD development, appears to be superior than plasma Aβ and t‐tau for defining cognitive continuum in old age.