Noninvasive Treatment of Alzheimer's Disease with Scintillating Nanotubes

Effective and accessible treatments for Alzheimer's disease (AD) are urgently needed. Soluble A beta oligomers are identified as neurotoxic species in AD and targeted in antibody-based drug development to mitigate cognitive decline. However, controversy exists concerning their efficacy and safety. In this study, an alternative strategy is proposed to inhibit the formation of A beta oligomers by selectively oxidizing specific amino acids in the A beta sequence, thereby preventing its aggregation. Targeted oxidation is achieved using biocompatible and blood-brain barrier-permeable multicomponent nanoscintillators that generate singlet oxygen upon X-ray interaction. Surface-modified scintillators interact selectively with A beta and, upon X-ray irradiation, inhibit the formation of neurotoxic aggregates both in vitro and in vivo. Feeding transgenic Caenorhabditis elegans expressing human A beta with the nanoscintillators and subsequent irradiation with soft X-ray reduces A beta oligomer levels, extends lifespan, and restores memory and behavioral deficits. These findings support the potential of X-ray-based therapy for AD and warrant further development.