Neurons (shown above) are progressively degraded in Alzheimer’s Disease. [Image: neurons/Mike Seyfang under CC-BY licence]

Recent findings from Duke University have implicated overactive immune cells as a potential cause of Alzheimer’s disease (AD).  The authors of this new study propose that AD can develop when immune cells in the brain overconsume an essential nutrient called arginine.  Previous research in this field has primarily studied amyloid, the protein that composes the characteristic plaques found in the brains of AD patients.  Focusing on the factors that cause these plaques to form, however, can provide a fresh perspective on a problem that has largely stumped the scientific community for decades.

While this discovery furthers our understanding of amyloid plaque formation, many more questions must be answered before a clinically relevant therapeutic can be developed.  The researchers used a drug called difluoromethylornithine (DFMO) to prevent immune cells in mice from consuming arginine, but this drug is unsuitable for long-term administration due to the development of hearing loss and other debilitating side effects.  In fact, any drug that blocks immune cell metabolism in this fashion will require a precisely tuned dose to obtain therapeutic efficacy while minimizing adverse effects.  Furthermore, it remains unclear how these results in mice will translate to human biology; predictably, mouse-based models of disease are often imperfect simulations of human pathology.  Additional research will determine if this strategy can produce a much-needed breakthrough in AD therapy or if this is simply a case of teaching an old drug to do new tricks.

Acknowledgments: Many thanks to Dr. Zarko Boskovic, HHMI Postdoctoral Fellow in the Department of Chemistry and Chemical Biology at Harvard University, for providing his expertise and commentary on the topic.

Managing Correspondent: Christopher Gerry

Original article: Arginine Deprivation and Immune Suppression in a Mouse Model of Alzheimer’s DiseaseThe Journal of Neuroscience

Media coverage: Alzheimer’s May Be Caused by Misfiring Immune System, Study Suggests – Time

Related SITN article: Protein Treatment for Alzheimer’s Disease?