mirADAM · Blood microRNAs ADAM10-target: novel diagnostic and prognostic biomarkers for Alzheimer's disease by electrochemical sensors

ADAM10 (A Disintegrin and Metalloprotease 10), the main α-secretase of the non-amyloidogenic cleavage of the amyloid precursor protein (APP), is a common player in Type 2 diabetes (T2D) and Alzheimer´s disease (AD). ADAM10 levels are altered in platelets, plasma, serum, and CSF of elderly with AD, suggesting its potential role as an AD biomarker. It is well known that there is an association between impaired insulin signaling and the amyloid cascade, as ADAM10 is also increased in T2D and insulin increases the expression and activity of this protease. However, few studies present efforts to understand the regulation of miRNAs ADAM10-targeted in these diseases, and its application on electrochemical sensors. This proposal aims to explore and validate circulating miRNAs that are deregulated, directly related to the pathophysiology of AD, T2D, or AD+T2D, and are ADAM10-targeted, as well as to assess the value of specific miRNAs panels on the diagnosis and prognosis of AD, leading to the application of these findings on a diagnostic device. All ethical aspects involved will be respected. Frozen serum samples will be provided from biorepositories and by a biobank. RT-qPCR assays will be performed for serum miRNAs screening differentially expressed in healthy control, T2D, AD, and T2D+AD subjects. Then, miRNA cross-sectional validation studies will be designed, and the capability of accurately detecting these miRNAs in a microfluidic platform will be tested. Data analysis will be conducted through ANCOVA, conditional logistic regression, and panels of ROC curves. This proposal attempts to provide evidence regarding the role of ADAM10 as a relevant link between two diseases of pandemic proportions, whilst identifying specific blood miRNAs ADAM10-targeted with diagnostic and prognostic potential to AD, leading to the application of these findings on a diagnostic device, highlighting its advantages as a less invasive, easier, faster, and lower-cost proceeding.