Alpha‐secretase ADAM10 as a blood‐based biomarker in Alzheimer’s disease and type 2 diabetes mellitus

Abstract

AbstractBackgroundAD (Alzheimer’s disease) is a progressive neurodegenerative disease characterized by extensive neuronal losses and deposits of neurofibrillary tangles and senile plaques. Patients with T2DM (type 2 diabetes mellitus) have structural brain changes and cognitive impairment, with a high risk of developing AD. These data suggest that insulin may play a key role in brain activity and memory formation. Based on these findings, AD has been called by some researchers T3DM (type 3 diabetes mellitus) or cerebral diabetes. Our group has been studying peripheral biomarkers for AD since 2010. Among them, our focus is the study of ADAM10 (A Disintegrin And Metalloprotease), an α‐secretase that inhibits the formation of senile plaques and, therefore, is protective against AD. We observed that this protein is decreased in platelets and increased in plasma of elderly people with this dementia compared to cognitively healthy elderly people.MethodThe participants of this research were people aged 60 or over, divided into 4 groups: participants with AD, participants with T2DM, participants with AD and concomitant presence of T2DM and cognitively unimpaired (CU) controls with regular plasma glucose levels. In this work, due to the COVID‐19 pandemic, we are presenting the results of a pilot trial carried out with data collected from 9 participants in each group. Patients’ blood was collected and plasma was used in assays to determine ADAM10 levels using an ADAM10‐specific Enzyme‐Linked Immunosorbent Assay (ELISA) kit (Life Sciences, catalog number LS‐F23768). Results were confirmed using SDS‐PAGE followed by western blotting analyses with the primary antibody anti‐ADAM10 (Ab39180 rabbit, Abcam). A “young control” performed with plasma samples from a young donnor and soroalbumin bands were used as endogen controls to avoid interassay biases in the densitometry analyses.ResultPlasma ADAM10 was elevated in persons with AD and T2DM and these levels were even higher when plasma from patients with both diseases was analysed.ConclusionThis study shows a clinical impact related to a new approach that could be used in the treatment of AD, also observing the metabolic and inflammatory states of the patients. Study also contributes to a better understanding of the biology of the disease itself.