Researchers at Kindai University report that oral arginine, a common amino acid, suppresses amyloid‑β aggregation and its toxic effects in fruit fly and mouse models of Alzheimer’s disease. In treated animals, amyloid buildup fell, inflammation markers dropped, and behavioral performance improved, suggesting arginine could be a low‑cost candidate for drug repurposing.
Alzheimer’s disease is one of the leading causes of dementia worldwide and currently has no definitive cure. While antibody drugs targeting amyloid‑β (Aβ) have recently been approved, their clinical benefits remain limited and they can be expensive and associated with immune‑related side effects. Researchers are therefore exploring simpler, safer, and more affordable approaches.
In a new study from Kindai University in Osaka, Japan, scientists investigated the potential of the amino acid arginine as a way to limit Aβ pathology. The work, led by graduate student Kanako Fujii, Professor Yoshitaka Nagai of the Department of Neurology at the Kindai University Faculty of Medicine, and Associate Professor Toshihide Takeuchi of the Life Science Research Institute, was published online on October 30, 2025, in Neurochemistry International.
Using in vitro assays, the team first showed that arginine can inhibit the formation of Aβ42 aggregates in a concentration‑dependent manner. They then evaluated oral arginine administration in two established Alzheimer’s disease models:
- A Drosophila model expressing Aβ42 with the Arctic mutation (E22G)
- An App^NL‑G‑F knock‑in mouse model carrying three familial Alzheimer’s‑related mutations
According to the study, arginine treatment in both models significantly reduced Aβ accumulation and alleviated Aβ‑induced toxicity.
In the mouse model, oral arginine decreased amyloid plaque deposition and lowered insoluble Aβ42 levels in the brain. Arginine‑treated mice also performed better in behavioral tests and showed reduced expression of pro‑inflammatory cytokine genes associated with neuroinflammation. These findings indicate that arginine’s protective effects extend beyond simply slowing aggregation and may include broader neuroprotective and anti‑inflammatory actions.
"Our study demonstrates that arginine can suppress Aβ aggregation both in vitro and in vivo," Prof. Nagai is quoted as saying in a Kindai University release. "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 authors frame their work as an example of drug repositioning—repurposing existing, clinically used compounds for new therapeutic indications. Arginine is approved for clinical use in Japan and is considered to have a favorable safety profile and adequate brain permeability in the contexts in which it is already used. However, the researchers stress that the dosing regimens in this study were optimized for experimental purposes and do not correspond to commercially available supplements.
They also emphasize that further preclinical and clinical research will be necessary to determine whether the benefits seen in Drosophila and mice translate to people with Alzheimer’s disease and to establish appropriate doses and treatment protocols. The study, supported by grants from Japan’s Ministry of Education, Culture, Sports, Science and Technology and other funding bodies, highlights a potentially cost‑effective path toward more accessible therapies targeting protein aggregation in neurodegenerative disorders.
