Towards Non-Invasive Diagnostic Imaging of Early-Stage Alzheimer’s Disease

One way to image the molecular pathology in Alzheimer’s disease (AD) is by positron emission tomography using probes that target amyloid fibrils. However, these fibrils are not closely linked to the development of the disease. It is now thought that early stage biomarkers that instigate memory loss comprise of Aβ oligomers (AβOs). Here we report a sensitive molecular magnetic resonance imaging (MRI) contrast probe that is specific for AβOs. We attach oligomer-specific antibodies onto magnetic nanostructures and show the complex is stable and it binds to AβOs on cells and brain tissues to give a MRI signal. When intranasally administered to an AD mouse model, the probe readily reached hippocampal AβOs. In isolated samples of human brain tissue, we observed an MRI signal that distinguished AD from controls. Such nanostructures that target neurotoxic AβOs are potentially useful for evaluating the efficacy of new drugs and ultimately for early-stage AD diagnosis and disease management.