Simple amino acid supplement greatly reduces Alzheimer’s damage

A new study published in Neurochemistry International reports that researchers from Kindai University and partner institutions found that oral arginine, a naturally occurring amino acid that acts as a safe chemical chaperone, can markedly reduce Aβ aggregation and its toxic effects in animal models of AD. The team noted that although arginine is sold as a dietary supplement, the dose and schedule used in their experiments were designed for research and do not match commercial products.

The project was led by Graduate Student Kanako Fujii and Professor Yoshitaka Nagai from the Department of Neurology, Kindai University Faculty of Medicine, Osaka, along with Associate Professor Toshihide Takeuchi from the Life Science Research Institute, Kindai University, Osaka.

Laboratory and Animal Tests Show Strong Anti-Amyloid Activity

Initial in vitro experiments demonstrated that arginine slows the formation of Aβ42 aggregates in a concentration-dependent fashion. Building on this evidence, the researchers tested oral arginine in two widely used AD models:

• A Drosophila model, expressing Aβ42 with the Arctic mutation (E22G)
• An App^NL-G-Fknock-in mouse model, carrying three familial AD mutations

In both systems, arginine treatment led to a significant drop in Aβ buildup and reduced the harmful effects associated with Aβ exposure.

"Our study demonstrates that arginine can suppress Aβ aggregation both in vitro and in vivo," explains Prof. Nagai. "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."

Benefits Extend Beyond Amyloid Reduction

In the mouse model, oral arginine lowered amyloid plaque formation and reduced insoluble Aβ42 levels in the brain. Mice receiving arginine also performed better in behavioral assessments and showed decreased expression of pro-inflammatory cytokine genes linked to neuroinflammation, a key contributor to AD progression. These results indicate that arginine's benefits may involve not only preventing aggregation but also providing broader neuroprotective and anti-inflammatory effects.

"Our findings open up new possibilities for developing arginine-based strategies for neurodegenerative diseases caused by protein misfolding and aggregation," notes Prof. Nagai. "Given its excellent safety profile and low cost, arginine could be rapidly translated to clinical trials for Alzheimer's and potentially other related disorders."

Repurposing Existing Compounds for Alzheimer's Treatment

This research highlights the advantages of drug repositioning, a strategy that repurposes existing safe compounds for new therapeutic uses. Because arginine is already approved for clinical use in Japan and shows good brain permeability, it may bypass multiple early hurdles that often slow traditional drug development.

The researchers stress that additional preclinical and clinical studies are essential to confirm whether these effects will translate to humans and to determine appropriate dosing strategies. Even so, the results present strong proof of concept that basic nutritional or pharmacological supplementation could reduce amyloid pathology and improve neurological health.

A Cost-Effective Approach With Global Potential

The study deepens scientific understanding of how Aβ aggregation occurs and presents a practical approach that could be implemented at scale. Its findings point to a cost-effective, readily available strategy that may one day support people affected by AD across the globe.

This work was supported by the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) (Grant No. 20H05927), Japan Society for the Promotion of Science (JSPS) (Grant Nos. 24H00630, 21H02840, 22H02792, and 25K02432), Japan Science and Technology Agency (JST) Super-Highway Program (SHW2023-03), and National Center of Neurology and Psychiatry.