Oral Arginine Shows Promise in Reducing Alzheimer’s Amyloid Buildup

Alzheimer’s disease (AD), a leading cause of dementia, continues to pose significant challenges worldwide. As researchers seek effective treatments, a new study reveals that oral administration of arginine, a naturally occurring amino acid, can effectively reduce amyloid β (Aβ) aggregation in animal models of AD. This promising research, published online on October 30, 2025, in the journal Neurochemistry International, was conducted by scientists from Kindai University and its collaborative institutions.

The study emerges amid ongoing efforts to find safer and more accessible therapies for AD. Current antibody-based treatments targeting Aβ have shown limited clinical effectiveness and can be costly, often accompanied by immune-related side effects. The findings from Kindai University suggest that arginine, which is available as an over-the-counter dietary supplement, could offer an alternative pathway for treatment.

Research Methodology and Findings

The research team, including Graduate Student Kanako Fujii and Professor Yoshitaka Nagai, conducted in vitro assays to demonstrate that arginine inhibits the formation of Aβ42 aggregates in a concentration-dependent manner. Following these promising results, they evaluated the effects of oral arginine in two established AD models: a Drosophila model expressing Aβ42 with the Arctic mutation and an App NL-G-F knock-in mouse model, which carries three familial AD mutations.

In both models, the administration of arginine significantly reduced Aβ accumulation and alleviated toxicity associated with the peptide. “Our study demonstrates that arginine can suppress Aβ aggregation both in vitro and in vivo,” noted Professor Nagai. The findings indicated that oral arginine not only decreased amyloid plaque deposition but also lowered insoluble Aβ42 levels in the brain.

In addition to the biochemical effects observed, arginine-treated mice exhibited improved behavioral performance and a reduction in the expression of pro-inflammatory cytokine genes linked to neuroinflammation—a key pathological feature of AD. These results suggest that arginine’s protective effects extend beyond mere aggregation inhibition, potentially encompassing broader neuroprotective and anti-inflammatory actions.

Implications for Alzheimer’s Treatment

The implications of this research are significant. Professor Nagai remarked, “What makes this finding exciting is that arginine is already known to be clinically safe and inexpensive, making it a highly promising candidate for repositioning as a therapeutic option for AD.” The researchers emphasize that arginine’s existing clinical use in Japan and its demonstrated safety profile could facilitate a faster transition to clinical trials, addressing barriers typically faced in traditional drug development.

The study advocates for the repositioning of existing, safe compounds for new therapeutic uses as an efficient pathway toward accessible Alzheimer’s treatments. Further preclinical and clinical studies will be necessary to evaluate whether these therapeutic effects can be replicated in humans and to determine optimal dosing regimens.

In conclusion, this research not only enhances understanding of Aβ aggregation dynamics but also suggests that simple nutritional or pharmacological supplementation could mitigate amyloid pathology and improve neurological outcomes. As the global population affected by Alzheimer’s continues to grow, findings such as these offer hope for more effective and accessible therapeutic strategies.