ADAM10 plasma levels predict worsening in cognition of older adults: a 3-year follow-up study

Abstract

Background: Blood-based biomarkers for Alzheimer’s disease (AD) are highly needed in clinic practice. So far, the gold standards for AD diagnosis are brain neuroimaging and beta-amyloid peptide, total tau and phosphorylated tau in cerebrospinal fluid (CSF), however, they are not attractive for large-scale screening. Blood-based biomarkers will allow an initial large-scale screening of patients under suspicion that could later be tested for the already established CSF biomarkers. To this regard, we and other research groups have already described that the plasma and platelet levels of ADAM10 are higher or lower, respectively, in patients with AD, compared to those cognitively healthy. Methods: This was a three-year longitudinal cohort study that included 219 community-dwelling older adults. Sociodemographic, clinical, lifestyle, depressive symptoms (GDS) and cognitive data (Mini-Mental State Examination, MMSE; Clock Drawing test, CDT) were gathered. The measurement of ADAM10 plasma levels was performed using a sandwich ELISA kit. Bivariate comparisons between groups were performed using Wilcoxon-Mann-Whitney for continuous data and Pearson’s chi-square tests with Yates continuity correction, for categorical data. Longitudinal analyzes of changes in the MMSE score were performed using Linear Mixed-Effects modeling.Results: Baseline MMSE score and ADAM10 values were significantly associated with MMSE score values on the follow-up assessment. When analyzing the interaction with time, having a normal MMSE at baseline and ADAM10 plasma levels presented a significant and independent negative association with MMSE score values on the follow-up assessment. The analyses also showed that the effect of ADAM10 plasma levels on decreasing MMSE score values on follow-up seems to be more pronounced in those with normal MMSE at baseline. Taken together, these results provide the first direct evidence that changes in ADAM10 plasma levels are predictors of cognitive worsening in older adults.Conclusions: Considering that ADAM10 increase in plasma is detected as soon as in mild cognitive impairment (MCI) patients, the results presented here may support the complementary clinical use of this biomarker, in addition to the classical AD biomarkers. Moreover, this work can shed light on the study of blood biomarkers for AD and contribute to the advancement of the area.

ADAM10 Plasma and CSF Levels Are Increased in Mild Alzheimer’s Disease

“…Importantly, a recent 3-year follow-up longitudinal work from our group revealed the predictive effect of increased ADAM10 plasma levels to diagnose impaired cognition, as supported by the decrease in the MMSE score values in the follow-up, which seems to be more significant in those with normal MMSE at baseline. On the other hand, in patients with already altered MMSE scores at baseline, ADAM10 did not act as a predictor of worse cognition in the follow-up assessment [ 43 ]. In this regard, the evaluation of ADAM10 plasma levels in patients with suspected cognitive decline may allow early interventions that could retard or even prevent the onset of AD.…”