A multidisciplinary approach for the early diagnosis of Alzheimer's disease and potential therapeutic applications

This thesis presents a multidisciplinary approach to improve Alzheimer's disease (AD) early diagnosis and therapy. The first part, based on the PRAMA cohort, identifies two novel CSF biomarkers using biophysical and cell viability assays to detect proteostasis failure. The second part focuses on the single-domain antibody DesAb-O, demonstrating its ability to selectively detect Aβ42 oligomers and neutralize their toxicity in patient-derived CSF. This tool was further engineered into Dimeric-DesAb-O. In the third part, ELISA, ThT, and TEM analyses confirm that dimerization enhances binding avidity, alters fibril morphology, and increases protective efficacy at low concentrations. This study suggests innovative immunodiagnostic and therapeutic strategies for future AD clinical applications. Liliana Napolitano is a researcher specializing in Alzheimer's disease and other neurodegenerative disorders. Her work focuses on the Aβ42 oligomer proteotoxicity and the engineering and validation of single-domain

Neurologia e neurofisiologia clinica.

447286 characters