BPS2026 – Naturally occurring betanin modulates oligomer formation of Alzheimer’s disease amyloid-β protein

In 2024, persons caring for individuals with Alzheimer’s disease (AD) contributed over 19 billion hours of unpaid assistance. The seventh leading cause of death in the United States, AD is a neurodegenerative disorder distinguished by the deposition of amyloid-β (Aβ) into senile plaques in the brain. Among the few available therapeutics, cholinesterase inhibitors and N-methyl D-aspartate (NMDA) receptor antagonists strictly target symptoms. In contrast, monoclonal antibodies may counteract biochemical origins of AD but are expensive. Increasing attention to small-molecule inhibitors of Aβ aggregation—especially those natural and widely available—aims to maximize the accessibility of AD treatment options worldwide. In this work, a red-beet pigment and polyphenol analog, betanin, is examined for anti-Aβ aggregation action, specifically inhibiting the formation of oligomers: soluble, intermediary aggregates well-established as the most neurotoxic conformation of Aβ. Anti-aggregation phenomena by 500 μM betanin treatment on Aβ oligomer formation are evidenced by 4,4'-dianilino-1,1'-binaphthyl-5,5'-disulfonic acid ( bis -ANS) spectroscopy to evaluate oligomer conformation, atomic force microscopy (AFM) to evaluate average oligomer size, and SDS-PAGE with western blot to evaluate the order of oligomer aggregation. The bis -ANS spectra demonstrate greater fluorescence of Aβ oligomers formed in the presence of betanin ( p < 0.01), relative to control (buffer alone), indicating an alteration of conformation for oligomers formed in the presence of betanin. AFM reveals a decrease in average size of oligomers formed in the presence of betanin ( p < 0.05), and western blots establish a shift in the order of Aβ oligomers toward smaller species among those formed in the presence of betanin. Altogether, these findings differentiate Aβ oligomers prepared with betanin as smaller and altered in conformation. Future cell culture and animal studies will reveal the impact of these changes on Aβ oligomer neurotoxicity and AD pathology.