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 allow an initial large-scale screening of patients under suspicion that could later be tested for the already established CSF biomarkers. To this regard, in this study, we evaluated whether plasma ADAM10 levels would be predictors of declines in cognition in community-dwelling older adults after a 3-year period follow-up. Methods This was a 3-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 scores were performed using linear mixed-effects modeling. Results Baseline MMSE scores and ADAM10 levels were significantly associated with MMSE scores on the follow-up assessment. When analyzing the interaction with time, normal MMSE scores and the ADAM10 plasma levels at baseline presented a significant and independent negative association with MMSE score values on the follow-up assessment. The analyses also showed that the predictive effect of ADAM10 plasma levels on decreasing MMSE scores on follow-up seems to be more pronounced in participants with normal MMSE, when compared with those with altered MMSE scores at baseline. 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. Taken together, these results provide the first direct evidence that changes in ADAM10 plasma levels are predictors of cognitive worsening in older adults. Moreover, this work can shed light on the study of blood biomarkers for AD and contribute to the advancement of the area.

ADAM10 Gene Variants in AD Patients and Their Relationship to CSF Protein Levels

“…We found significant single differences in some of the kits comparing AD and controls (toward higher levels in the AD group), with male patients exhibiting higher levels than females, or early-onset AD cases showing higher levels than late-onset patients. Increased CSF and plasma levels in mild AD cases has been reported by Pereira Vatanabe et al [ 19 ], and a prospective study suggests that higher baseline plasma levels are predictive of cognitive decline [ 33 ]. The higher ADAM10 levels found in men could be meaningful considering AD is more prevalent among women; this result could be interpreted as suggestive of a protective biochemical phenotype in males.…”

Shifting the balance: soluble ADAM10 as a potential treatment for Alzheimer's disease

“…This was found to be correlated with lower levels of APP processing in the non-amyloidogenic pathway as evidenced by reduced sAPPα (Agüero et al, 2020 ). In a longitudinal study of older adults, low levels of active ADAM10 correlated with a decline in cognitive abilities (Oliveira Monteiro et al, 2021 ). Moreover, ADAM10 is interrelated to the disease as levels of ADAM10 are reduced in AD patients (Colciaghi et al, 2002 , 2004 ).…”

Effect of type 2 diabetes on A disintegrin and metalloprotease 10

“…Changes in plasma levels of ADAM10 have been shown to predict the deterioration of cognitive function in older adults. 26 Serum ADAM10 levels have also been evaluated as a biomarker for malignancy like colorectal cancer. 27 In diabetes, it has been suggested that urinary ADAM10 might be a biomarker of early diabetic nephropathy.…”