Duas doenças de Alzheimer - Diagnóstico de tipos distintos de doença de Alzheimer no LCR e plasma

Alzheimer's Disease (AD) is a major challenge in modern healthcare, characterized by its progressive cognitive decline and profound impact on individuals and families alike. Despite decades of rigorous clinical trials and scientific advances in disease knowledge, no treatment has yet been discovered to significantly mitigate the irreversible course of the disease(5). This failure underscores the complexity inherent in AD pathology and treatment and opens new research lines to better characterize and understand the disease. Our(2) and others(1) recent findings suggest that the clinical presentation of AD may encompass biologically distinct disease subtypes, contributing to the challenges in developing effective therapeutic interventions. This hypothesis challenges traditional notions of AD as a singular entity and underscores the need for tailored approaches to diagnosis and treatment. With this in mind, the current project aims to develop and validate a straightforward and practicable method for identifying distinct subtypes of AD using plasma samples. This goal arises because current methods for diagnosis and treatment do not consider the differences that exist within AD. To reach this primary goal, the project focus on these specific objectives: Method Development: The research aims to develop a simple and feasible method, allowing for the identification of AD subtypes through the analysis of plasma samples. By translating biomarkers identified from CSF analysis to plasma samples using targeted proteomics, untargeted proteomics, and metabolomics approaches, the research aims to establish a robust foundation for subtype identification. Validation of Biomarkers using a larger cohort: A new and larger cohort will be classified using our CSF biomarkers, and plasma samples will be characterized using the previously developed methods and new machine learning approaches proposed in the project. The plasma biomarkers will be validated, ensuring the reliability and reproducibility of the proposed method across diverse populations. This phase of the research is crucial for establishing the clinical utility and scalability of the developed approach. Improving the Process: Recognizing the importance of fast and affordable diagnosis and treatment for managing AD, this project focus on speeding up sample analysis by developing a method that cuts down the current analysis time, aiming to handle larger groups of samples and perform analysis in various labs. This process is critical to develop a service able to help clinical decisions, thus having both a social and an economic impact. After the project's completion, we aim to establish a certified service offering precise quantification of the targeted proteins. This quantification will be achieved through antibody-based assays, such as ELISA, or alternatively, via Multiple Reaction Monitoring Mass Spectrometry based assays in cases where developing cost-effective ELISA assays proves unfeasible. Altogether, this project will be critical in advancing our understanding of AD heterogeneity with high potential use in guiding personalized treatment strategies.