ADAM10 as a biomarker for Alzheimer’s disease

Abstract Sensitivity, specificity, and ease of use are the most important factors in a biomarker. It has been demonstrated that cerebrospinal fluid (CSF) biomarkers present sensitivity and specificity of 85%–90% to identify prodromal Alzheimer’s disease (AD) in the mild cognitive impairment stage. However, CSF collection is an uncomfortable, invasive, and expensive analysis. Related to biomarkers in blood, positive results have been found for some proteases, especially BACE1 and ADAM10. Our results indicate that active ADAM10 is decreased in platelets of AD patients and that this reduction is intensified with the progress of the disease. We hypothesized that when anchored in the platelet membrane, ADAM10 presents enzymatic activity and when soluble in plasma, CSF, and serum, the enzyme is inactive. In addition, the plasma ADAM10 levels were found to be increased in older people with AD and MCI compared to cognitively healthy controls. These levels can be used as an easy way to aid AD diagnosis. Future studies should provide evidence that the transmembrane domain and consequent release of ADAM10 from the plasma membrane are responsible for its inactivity in APP cleavage.