This section focuses on the application of the single-domain antibody DesAb-O as a tool for detecting and neutralizing toxic Aβ42 oligomers. Through in vitro ELISA and dot-blot assays, the study demonstrates that DesAb-O selectively detects synthetic Aβ42 oligomers and recognizes them within the complex matrix of cerebrospinal fluid (CSF) from Alzheimer’s Disease patients. Utilizing STED microscopy, the study further characterizes the antibody’s ability to identify oligomers bound to neuronal membranes and internalized into the cytosol. Crucially, the chapter provides evidence that DesAb-O inhibits the interaction between toxic aggregates and the SH-SY5Y cells, thereby preventing mitochondrial dysfunction, membrane destabilization, and neuronal impairment induced by both synthetic species and patient-derived CSF.