Development of biomarkers for amyloid plaques: relevance for the study of Alzheimer's Disease

• Grant number: 10/20197-5
• Support Opportunities: Research Grants - Young Investigators Grants
• Start date: June 01, 2011
• End date: May 31, 2015
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Luciana Malavolta Quaglio
• Grantee: Luciana Malavolta Quaglio
• Host Institution: Faculdade de Ciências Médicas da Santa Casa de São Paulo (FCMSCSP). Fundação Arnaldo Vieira de Carvalho. São Paulo , SP, Brazil
• Associated researchers: Antonio Claudio Tedesco ; Barbara Szot Marczewski Lopes ; Francisco Romero Cabral ; Hudson de Sousa Buck ; Tânia Araújo Viel
• Associated scholarship(s): 14/01452-5 - Interpretation of the formation of amyloid fibrils by peptide sequences: relevance to Alzheimer's Disease and type 2 Diabetes, BP.IC

Abstract

The best known diseases related to peptide aggregation are Alzheimer's, Type II Diabetes, Prion-related Encephalopathies, Huntington´s and Parkinson's, all referred by the general term amyloidosis which is characterized by the deposition of amyloid fibrils in specific tissues, these aggregates being the causative agents of several types of degeneration. This project aims at studying the molecular diagnosis of these pathological conditions and the mechanisms by which amyloid fibrils are formed in the brain of people affected by Alzheimer's disease through the development of biomarkers. The first part of the project comprises the chemical and physical steps for the synthesis, radiolabeling and encapsulation of some specific peptides. These will be carried out to further assess the ability of these synthesized peptides to interact with the beta-amyloid fibrils (1-42), the main responsible for the formation of amyloid plaques. The second stage has biological implications, being performed in experimental animals where the interaction of the synthetic peptides with amyloid fibrils will be assessed by their binding affinity, using brain homogenates obtained from transgenic mice presenting Alzheimer's disease. In parallel, we will perform in vivo animal studies to evaluate the biodistribution and the blood brain barrier permeability of the peptides of interest in specific organs by CT imaging, using single photon emission (SPECT). It is important to mention the value of early detection and the understanding of amyloid plaques formation for a more specific pharmacological approach of the Alzheimer's disease, which affects millions of people worldwide. (AU)