Oral Arginine Shown to Reduce Amyloid Buildup in Alzheimer’s Models

Alzheimer’s disease (AD), a significant cause of dementia globally, remains without a definitive cure. Recent advancements in antibody-based therapies targeting amyloid β (Aβ) have shown limited clinical effectiveness, highlighting the need for safer and more accessible treatments. A study published on October 30, 2025, in Neurochemistry International, reveals that oral administration of arginine, a naturally occurring amino acid, can effectively suppress Aβ aggregation and its harmful effects in animal models of AD.

The research team from Kindai University, including Graduate Student Kanako Fujii and Professor Yoshitaka Nagai, collaborated with Associate Professor Toshihide Takeuchi to optimize the dosage and administration of arginine for research purposes. While arginine is available as an over-the-counter dietary supplement, its specific formulation in this study differs from commercially available versions.

Study Findings and Implications

Using in vitro assays, the researchers demonstrated that arginine inhibits Aβ42 aggregate formation in a concentration-dependent manner. They then evaluated the effects of oral arginine in two established AD models: a Drosophila model expressing Aβ42 with the Arctic mutation (E22G) and an App NL-G-F knock-in mouse model carrying three familial AD mutations. In both models, arginine administration significantly reduced Aβ accumulation and alleviated Aβ-induced toxicity.

“Our study demonstrates that arginine can suppress Aβ aggregation both in vitro and in vivo,” explained Professor Nagai. He added, “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.”

In the mouse model, oral arginine not only decreased amyloid plaque deposition but also lowered insoluble Aβ42 levels in the brain. Mice treated with arginine exhibited improved behavioral performance and a reduction in the expression of pro-inflammatory cytokine genes associated with neuroinflammation, a key feature of AD pathology. These results suggest that arginine’s protective effects extend beyond simply inhibiting aggregation, offering broader neuroprotective and anti-inflammatory actions.

Potential for Future Research

The findings from this study open new avenues for developing arginine-based strategies aimed at neurodegenerative diseases associated with protein misfolding and aggregation. Professor Nagai noted, “Given its excellent safety profile and low cost, arginine could be rapidly translated to clinical trials for Alzheimer’s and potentially other related disorders.”

The research underscores the potential of drug repositioning, which involves repurposing existing, safe compounds for new therapeutic uses, as a viable approach to accessible treatments for Alzheimer’s. Since arginine is already clinically used in Japan and demonstrates high safety and brain permeability, it may overcome several early barriers that traditional drug development encounters.

Further preclinical and clinical studies are necessary to determine if these therapeutic effects can be replicated in humans and to establish optimal dosing regimens. Nevertheless, the current findings provide compelling proof that simple nutritional or pharmacological supplementation could help mitigate amyloid pathology and enhance neurological outcomes.

This study not only enriches our understanding of Aβ aggregation dynamics but also highlights a feasible and cost-effective strategy that could benefit the growing global population affected by Alzheimer’s disease.