Diagnostic and predictive power of plasma proteins in Alzheimer's disease: a cross-sectional and longitudinal study in China

Abstract

Convenient and effective biomarkers are essential for the early diagnosis and treatment of Alzheimer's disease (AD). In the cross-sectional study, 103 patients with AD, 82 patients with aMCI and 508 normal controls (NC) were enrolled. The single-molecule array (Simoa) technique was used to assess the levels of plasma proteins, including NfL, T-tau, P-tau-181, Aβ40, Aβ42. Montreal Cognitive Assessment (MoCA) was used to assess the overall cognitive function of all subjects. Moreover, Amyloid PET and structural head MRI were also performed in a subset of the population. In the follow-up, the previous 508 normal older adults were followed up for two years, then COX regression analysis was used to investigate the association between baseline plasma proteins and future cognitive outcomes. NfL, T-tau, P-tau-181, Aβ40, Aβ42 and Aβ42/40 were altered in AD dementia, and NfL, Aβ42 and Aβ42/40 significantly outperformed all plasma proteins in differentiating AD dementia from NC, while NfL and Aβ42/40 could effectively distinguish between aMCI and NC. However, only plasma NfL was associated with future cognitive decline, and it was negatively correlated with MoCA (r = - 0.298, p < 0.001) and the volume of the left globus pallidus (r = - 0.278, p = 0.033). Plasma NfL can help distinguish between cognitively normal and cognitively impaired individuals (MCI/dementia) at the syndrome level. However, since we have not introduced other biomarkers for AD, such as PET CT or cerebrospinal fluid, and have not verified in other neurodegenerative diseases, whether plasma NFL can be used as a biomarker for AD needs to be further studied and explored.

Keywords: Alzheimer disease; Globus pallidus; NfL; Plasma proteins; Simoa.

Figure 1

Figure 1 Comparisons of plasma biomarker concentrations across different groups. This figure illustrates the differences in the expression of plasma proteins: Aββ42, Aββ40, Aββ42/40, T-tau, p-tau-181, and NFL in different cognitive states (NC, aMCI, and AD). Aβ42/40 amyloid-β42/40, AD Alzheimer's disease, Nc normal controls, aMCI amnestic mid cognitive impairment, NfL neurofilaments light, P-tau181 phosphorylated tau 181, T-tau total tau. *p<0.05.

Figure 2

ROC curve was used to compare the accuracy of plasma proteins in the diagnosis of aMCI and AD. This figure shows the predictive power of different plasma proteins (Aββ42, Aββ40, Aββ42/40, T-tau, p-tau-181, and NFL) for aMCI and AD. Aβ42/40 amyloid-β42/40, AD Alzheimer's disease; Nc normal controls, aMCI amnestic mid cognitive impairment, NfL neurofilaments light, P-tau181 phosphorylated tau 181, T-tau total tau.