ADAM10 secretase levels and activity in patients with type 2 Diabetes mellitus and Alzheimer's Disease

• Grant number: 19/26709-2
• Support Opportunities: Scholarships in Brazil - Master
• Effective date (Start): April 01, 2020
• Effective date (End): February 28, 2022
• Field of knowledge: Health Sciences - Medicine - Psychiatry
• Principal Investigator: Márcia Regina Cominetti
• Grantee: Danielle dos Santos Maia Salheb de Oliveira
• Host Institution: Centro de Ciências Biológicas e da Saúde (CCBS). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil

Abstract

AD (Alzheimer's disease) is a gradual and progressive neurodegenerative disease characterized by predominant cortical atrophy in the medial temporal lobe, and microscopically, extensive neuronal losses and deposits called neurofibrillary tangles and senile plaques. From the results of the Rotterdam study in 1992, it is known that Diabetes mellitus type 2 (DM) increases the risk of dementia. Patients with T2DM 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. From these findings, AD has been called by some researchers "type 3 Diabetes" (DM3) 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 senile plaque formation and is therefore protective against AD, is decreased in platelets. of elderly people with this dementia compared with cognitively healthy elderly. In this sense, the aim of this study is to verify the levels and activity of ADAM10 among cognitively healthy subjects, with AD alone or with the concomitant presence of T2DM. 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 disease biology itself. (AU)