Immune cells may facilitate the development of Alzheimer's disease: study

Research data published in the Journal of Neuroscience suggest that the aberrant immune cell activity may promote the development of Alzheimer's disease. Study investigators uncovered in a mouse model that immune cells that normally protect the brain begin to consume arginine as the animals progressed toward an Alzheimer's disease state, while treatment with the compound difluoromethylornithine (DFMO) prior to the onset of symptoms prevented the formation of plaques.

In the study, the investigators used a previously developed mouse model named CVN-AD, in which a decline in immune-mediated nitric oxide levels results in the appearance of the characteristic features of Alzheimer's disease, such as amyloid deposition, behavioural changes and neuronal loss. The researchers observed that during the development of the disease, the mice exhibited elevated levels of CD11c microglia and extracellular arginase, resulting in reduced levels of arginine in the brain.

Meanwhile, the researchers found that CVN-AD mice treated with DFMO prior to the appearance of symptoms displayed fewer CD11c microglia and reduced plaque formation in their brains. The researchers also noted that the treated mice displayed less memory loss based on their performance in memory tests. "All of this suggests to us that if you can block this local process of amino acid deprivation, then you can protect -- the mouse, at least -- from Alzheimer’s disease," explained one of the study reaserchers Matthew Kan.

"We see this study opening the doors to thinking about Alzheimer's in a completely different way, to break the stalemate of ideas in AD," remarked study's senior author Carol Colton, adding "the field has been driven by amyloid for the past 15, 20 years and we have to look at other things because we still do not understand the mechanism of disease or how to develop effective therapeutics."

Commenting on the findings, James Pickett, head of research at the Alzheimer's Society, said that the study "joins some of the dots in our incomplete understanding of the processes that cause Alzheimer's disease." Pickett continued "these new findings reflect earlier observations that arginine is reduced in the brains of people with Alzheimer's disease," adding "the next step would be to show that targeting arginine metabolism in the brain can reduce the death of brain cells, as this was not shown in the current study."

Last month, the UK government announced the creation of a fund to support the development of treatment for dementias such as Alzheimer's disease, with backing by several drugmakers including Eli Lilly, GlaxoSmithKline, Johnson & Johnson and Pfizer. For related analysis, see ViewPoints: Can the Dementia Discovery Fund help pharma overcome its drastically poor record in Alzheimer's disease R&D?

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