Immune Molecule, IL-33, Seen to Reverse Alzheimer’s Pathology in Mouse Model

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by Magdalena Kegel |

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Gene therapy and Alzheimer’s disease

An immune molecule called IL-33 can reverse Alzheimer’s disease symptoms and cognitive decline in mice, researchers show in a study published in the journal Proceedings of the National Academy of Sciences (PNAS). The findings lend support to theories that humans have a natural defense against Alzheimer’s that decreases with age.

The study, IL-33 ameliorates Alzheimer’s disease-like pathology and cognitive decline,” was a joint effort by researchers from the University of Glasgow, Scotland, U.K., andHong Kong University of Science and Technology (HKUST). It used a mouse model of Alzheimer’s called APP/PS1.

These mice display both disease symptoms, such as cognitive decline, and the accumulation of amyloid-beta in their brains. Earlier studies have shown that patients with Alzheimer’s have low levels of IL-33, but researchers have not known what function the factor, that normally is particularly abundant in the central nervous system, plays in disease.

“We found that injection of IL-33 into aged APP/PS1 mice rapidly improved their memory and cognitive function to that of the age-matched normal mice within a week,” Eddy Liew, a University of Glasgow professor and one of the two senior researchers behind the study, said in a press release.

IL-33 injections also reduced amyloid-beta plaques in the mice brains, a finding that the researchers showed was linked to an increased mobilization of microglia against the plaques, engulfing and ingesting amyloids. The research team concluded that IL-33 likely induced this effect via the enzyme neprilysin, which is known to target soluble amyloid-beta oligomers that cause cell toxicity.

Results also demonstrated that the factor could reduce brain inflammation, a process that has been shown to speed up plaque formation in Alzheimer’s. For this reason, IL-33 might also prevent new plaques from forming.

“The relevance of this finding to human Alzheimer’s is at present unclear. But there are encouraging hints. For example, previous genetic studies have shown an association between IL-33 mutations and Alzheimer’s disease in European and Chinese populations. Furthermore, the brain of patients with Alzheimer’s disease contains less IL-33 than the brain from non-Alzheimer’s patients,” said Dr. Liew, taking a cautious stance toward the clinical implications of his findings.

“Exciting as it is, there is some distance between laboratory findings and clinical applications. There have been enough false ‘breakthroughs’ in the medical field to caution us not to hold our breath until rigorous clinical trials have been done. We are just about entering Phase I clinical trial to test the toxicity of IL-33 at the doses used,” he added. “Nevertheless, this is a good start.”