Summary: A new study from Kindai University demonstrates that oral arginine, a naturally occurring amino acid and clinical chemical chaperone, can substantially inhibit amyloid-β (Aβ) aggregation in laboratory and animal models of Alzheimer’s disease. The researchers report that arginine prevents Aβ42 from forming toxic aggregates, reduces plaque burden, and diminishes neuroinflammation in both fruit fly and mouse models carrying Alzheimer’s-related mutations.
Treated mice also showed measurable improvements in cognitive and behavioral tests, alongside lower levels of inflammatory cytokine expression in the brain. Because arginine is already regarded as clinically safe, inexpensive, and widely available, these results highlight its strong potential for therapeutic repurposing pending further preclinical and human studies.
Key Findings:
- Aggregation Inhibition: Arginine reduced Aβ42 aggregation in vitro in a concentration-dependent manner and suppressed aggregate formation in animal models.
- Neuroprotective Effects: Oral arginine lowered amyloid plaque deposition, reduced insoluble Aβ42 levels, decreased expression of pro-inflammatory cytokines, and improved behavioral outcomes in a knock-in mouse model.
- Translational Potential: Given its favorable safety profile and low cost, arginine is a promising candidate for rapid drug repositioning to treat Alzheimer’s disease and other protein-aggregation disorders.
Source: Kindai University
Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and a major cause of dementia worldwide. Recent antibody therapies targeting amyloid-β have produced modest clinical benefits but are costly and can trigger immune-related side effects. There is a pressing need for safer, affordable, and widely accessible strategies that slow Aβ aggregation or prevent its accumulation in the brain.
In a study published online on October 30, 2025 in Neurochemistry International, researchers from Kindai University and partner institutions evaluated whether orally administered arginine could reduce Aβ pathology. The team emphasized that, although arginine supplements are commercially available, the specific dosages and administration used in this research were optimized for experimental purposes and do not directly match over-the-counter formulations.
The research team included Graduate Student Kanako Fujii and Professor Yoshitaka Nagai from the Department of Neurology at Kindai University Faculty of Medicine, and Associate Professor Toshihide Takeuchi from the Life Science Research Institute at Kindai University.
Methods and Models
Researchers first applied in vitro assays to measure Aβ42 aggregation. These experiments showed a dose-dependent inhibition of aggregate formation when arginine was present. Building on the biochemical results, the team tested oral arginine in two established animal models of AD:
- A Drosophila model expressing Aβ42 with the Arctic mutation (E22G), which accelerates aggregation and toxicity
- An AppNL-G-F knock-in mouse model carrying three familial Alzheimer’s disease mutations that promote Aβ deposition
In both models, arginine administration substantially lowered Aβ accumulation and mitigated Aβ-related toxicity.
Results and Interpretation
In the AppNL-G-F knock-in mice, oral arginine significantly reduced amyloid plaque load and decreased levels of insoluble Aβ42 in the brain. These mice also exhibited improved performance on behavioral assays and showed reduced expression of cytokine genes associated with neuroinflammation—an important driver of neurodegeneration in AD.
Similarly, in the Drosophila Arctic Aβ42 model, arginine lowered Aβ42 accumulation in a dose-dependent manner and rescued phenotypes linked to Aβ toxicity. Taken together, these findings indicate that arginine’s benefits extend beyond simple aggregation blockade to broader neuroprotective and anti-inflammatory effects.
“Our data show that arginine can suppress Aβ aggregation both in vitro and in vivo,” says Prof. Yoshitaka Nagai. “Because arginine is already known to be clinically safe and inexpensive, it represents a promising candidate for therapeutic repositioning against Alzheimer’s disease.”
Clinical and Research Implications
These results support the concept of drug repositioning—using existing, well-tolerated compounds for new therapeutic purposes—as an efficient route toward accessible AD treatments. Arginine’s established clinical use in some countries and its brain permeability may help it overcome early translational barriers that stall many novel drug candidates.
However, the authors stress the need for additional preclinical studies to refine dosing and safety parameters, followed by carefully designed human clinical trials to determine whether the protective effects observed in animals can be replicated in people with or at risk for Alzheimer’s disease.
Overall, this study provides a compelling proof of concept that a simple amino acid supplement could help reduce amyloid pathology and improve neurological outcomes, potentially opening new avenues for treating AD and other neurodegenerative diseases driven by protein misfolding and aggregation.
Funding information: This research 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 the National Center of Neurology and Psychiatry.
Key Questions Answered:
A: In vitro assays and animal studies showed that arginine inhibits Aβ42 aggregation and reduces toxic amyloid buildup in model systems.
A: Arginine lowered plaque levels, decreased markers of neuroinflammation, and improved behavioral and cognitive measures in treated animals.
A: Arginine is inexpensive, has an established safety record, shows brain permeability, and could be rapidly repurposed pending clinical validation.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- The journal paper was reviewed in full.
- Additional context was added by staff to aid reader understanding.
About this supplements and Alzheimer’s disease research news
Author: Tamaki Kasuya
Source: Kindai University
Contact: Tamaki Kasuya – Kindai University
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Oral administration of arginine suppresses Aβ pathology in animal models of Alzheimer’s disease” by Kanako Fujii et al., Neurochemistry International.
Abstract
Oral administration of arginine suppresses Aβ pathology in animal models of Alzheimer’s disease
Antibody therapies targeting amyloid-β have advanced in recent years but remain limited by modest clinical benefit, high cost, and potential adverse effects. There is an urgent need for alternative, safe, and cost-effective approaches to prevent Aβ aggregation or its accumulation in the brain.
This study reports that arginine, a clinically used and well-tolerated chemical chaperone, suppresses Aβ aggregation both in vitro and in vivo. In biochemical assays, arginine inhibited aggregation of the Aβ42 peptide in a concentration-dependent manner. In a Drosophila model expressing Arctic (E22G) Aβ42, oral arginine reduced Aβ42 accumulation and rescued Aβ-mediated toxicity. In AppNL-G-F knock-in mice, arginine intake suppressed plaque deposition, lowered insoluble Aβ42, improved behavioral abnormalities, and reduced expression of neuroinflammation-associated cytokine genes.
These findings indicate that oral arginine reduces Aβ deposition and ameliorates Aβ-driven neurological phenotypes in animal models, supporting arginine’s potential as a safe, cost-effective candidate for rapid clinical translation to treat Alzheimer’s disease and related protein-aggregation disorders.