Evaluation of molecular changes associated with aging in the Down Syndrome animal model

Abstract

Down Syndrome (DS) is a genetic disorder on chromosome 21, which causes mental retardation, small mouth, drawn eyes, rounded head, and other characteristics. Individuals with DS have a high risk of developing Alzheimer's disease (AD), which is a neurodegenerative disease, characterized by the formation of senile plaques composed of beta-amyloid (A²). The life expectancy of SD patients has increased in recent decades, making aging a new and important area of study in DS. Positron Emission Tomography (PET) imaging is a very sensitive method for the detection of alterations, allowing the noninvasive study of cellular and molecular processes in vivo, being a very important tool in the understanding of the aging process, besides being a tool to aid in the diagnosis of neurological diseases. In this project, the aging process in DS will be analyzed by imaging (PET) using specific radiopharmaceuticals for evaluation of neuroinflammation, ²-amyloid plaque deposition and changes in white matter. These factors are altered in postmortem tissue analysis, but there were not yet evaluated by longitudinal in vivo imaging. The study of these parameters will be done in a temporal way, evaluating the changes throughout the life of the animal model of DS. The characterization of the alteration profile of these processes, as well as the correlation between them, may lead to the identification of critical moments for the initiation and therapeutic follow-up, or even development of new therapeutic interventions. (AU)