Analysis of 27 vascular-related proteins reveals that NT-proBNP is a potential biomarker for Alzheimer's disease and mild cognitive impairment: a pilot-study

Abstract

Alzheimer's disease (AD) is a severe neurodegenerative disease. Cerebrovascular changes often accompany AD-related pathology. Despite a considerable progress in the diagnostic accuracy of AD, no blood biomarkers have been established so far. The aim of the present study was to search for changes in plasma levels of 27 vascular-related proteins of healthy controls, patients with mild cognitive impairment (MCI) and AD. In a sample of 80 participants we showed that out of these 27 proteins, six proteins were slightly changed (up to 1.5×) in AD (alpha2-macroglobulin, apolipoprotein-A1, plasminogen activator inhibitor, RAGE, Tissue Inhibitors of Metalloproteinases-1 and Trombospondin-2) and one marker (serum amyloid A) was enhanced up to 6× but with a very high variance. However, N-terminal pro-brain natriuretic peptide (NT-proBNP) was significantly enhanced both in MCI and AD patients (1.9×). In a second analysis of a sample of 110 subjects including younger healthy controls, we confirmed that NT-proBNP has the potential to be a stable candidate protein for both diagnosis and AD disease progression.

Keywords: Alzheimer; Biomarker; Diagnosis; Mild cognitive impairment; Multiplex ELISA; NT-proBNP; Plasma.

Fig. 1

Plasma NT-proBNP levels of young healthy controls (yCo), old controls (oCo), patients with mild cognitive impairment (MCI) and Alzheimer’s disease (AD); see Table 1. Statistical analysis was performed by one way ANOVA with a subsequent Fisher PLSD posthoc test. Values in parenthesis give the number of analyzed subjects.

Fig. 2

Yearly conversion rates for plasma NT-proBNP levels from controls to mild cognitive impairment (CO to MCI) and MCI to Alzheimer’s disease (MCI to AD), as well as yearly changes in stable MCI (MCI–MCI) and stable AD (AD–AD). Values are given as mean ± SEM. The number in parenthesis gives the number of follow up patients. The groups were statistically compared against CO-MCI using one way ANOVA and a Fisher LSD posthoc test (*p < 0.05).

Fig. 3

(A) ROC curve based on NT-proBNP plasma levels for MCI patients vs. controls. (B) ROC curve based on NT-proBNP plasma levels for patients with Alzheimer dementia vs. controls.