Role of the insulin signaling pathway proteins and their relation with the secretase ADAM10 in Alzheimer's Disease

Abstract

AD (Alzheimer's disease) is a progressive neurodegenerative disease predominantly characterized by cortical atrophy in the medial temporal lobe, and microscopically, by extensive neuronal losses and deposits called neurofibrillary tangles and senile plaques. Since the results of the Rotterdam study in 1992, it is known that T2DM (type 2 diabetes mellitus) increases the risk of dementia. Patients with T2DM have structural brain alterations and cognitive impairment, with a high risk of developing AD. These data suggest that insulin may play a key role in relation to brain activity and memory formation. From these findings, AD has been called by some researchers of "type 3 diabetes" (TDM3) or "brain diabetes". Our group has been studying peripheral biomarkers for AD since 2010. Our results indicate that ADAM10 (A Disintegrin And Metaloprotease), the ±-secretase that inhibits the formation of senile plaques and is therefore protective against AD, is decreased in platelets of elderly people with this dementia, compared to cognitively healthy elderly. In this sense, the objective of this study is to verify if the differences in the ADAM10 levels between cognitively healthy subjects with MCI (Mild Cognitive Impairment) and AD with the concomitant presence of TDM2, as well as the effect of alterations of the insulin pathway in the levels and activities of this ±-secretase. The clinical impact of this study is related to a new approach that could be used in the treatment of this type of dementia, also observing the metabolic and inflammatory states of the patients, besides contributing to a better understanding of the biology of the disease itself. (AU)