Does neuroinflammation blockade modify Alzheimer's Disease? Experimental study with the triple-transgenic model.

• Grant number: 24/16270-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2024
• End date: May 31, 2025
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Principal Investigator: Luiz Roberto Giorgetti de Britto
• Grantee: Marina da Silva Meira Neta
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Alzheimer's disease (AD) is pathologically characterized by the deposition of beta-amyloid (¿A) protein plaques and neurofibrillary tangles (NFTs), in addition to an important involvement of neuroinflammation, leading to neuronal loss and functional consequences, as well as cognitive and behavioral changes. Recent research using phenotypic screening based on lipopolysaccharide (LPS)-induced microglial phenotype has identified a new molecule, named AD-16, described as an effective inhibitor of neuroinflammation. AD-16 suppresses the production of pro-inflammatory mediators and cytokines, such as interleukin 1¿ (IL-1¿) and tumor necrosis factor ¿ (TNF-¿), whereas stimulating cytokines with regulatory profiles, such as interleukin 4 (IL-4). Thus, in the present study, chronic treatment with AD-16 will be carried out in a triple-transgenic model for AD, seeking to analyze the behavioral aspects by performing the New Object Recognition Test (RO) and Passive Avoidance Test (PA). In addition, ¿-amyloid 1-16 staining will also be analyzed using an immunohistochemistry assay, to confirm the model and evaluate the effects of treatment with the neuroinflammatory inhibitor on the pathology. Inflammatory aspects will also be evaluated, using immunohistochemistry with Iba-1 staining, as well as performing the ELISA technique for quantitative analysis of some of the main cytokines involved in the neuroinflammatory process.