Protein research opens potential treatment of Alzheimer

In a potential breakthrough in treatment of Alzheimer's disease, researchers have discovered that a protein can reverse the devastating disease projected to affect nearly 65 million people globally by 2030.
The study was led by scientists at the University of Glasgow (UG) and the Hong Kong University of Science and Technology (HKUST).
The research, published today in Proceedings of the National Academy of Sciences USA (PNAS), was co-led by Professor Eddy Liew from the UG's Institute of Infection, Immunity and Inflammation and Professor Nancy Ip of HKUST.
The study has discovered that a protein called IL-33 can reverse Alzheimer's disease like pathology and cognitive decline in mice.

Alzheimer's disease is a devastating condition with no known effective treatment. It is the most common cause of dementia, affecting around 850,000 people in the UK, mainly over the age of 65. It affects 1/14 people in this age group and is increasing with the ageing population.
Globally, 65 million people are projected to develop Alzheimer's by 2030.

Professor Eddy Liew, Fellow of the Royal Society, who co- directed the research said, "Alzheimer's disease currently has an urgent unmet clinical need. We hope that our findings can eventually be translated into humans".
"IL-33 is a protein produced by various cell types in the body and is particularly abundant in the central nervous system (brain and spinal cord). We carried out experiments in a strain of mouse (APP/PS1) which develop progressive AD-like disease with ageing.

"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," Liew said.
The hallmarks of Alzheimer's include the presence of extracellular amyloid plaque deposits and the formation of neurofibrillary tangles in the brain. During the course of the disease, 'plaques' and 'tangles' build up, leading to the loss of connections between nerve cells and eventually to nerve cell death and loss of brain tissue.
IL-33 appears to work by mobilising microglia (immune cells in the brain) to surround the amyloid plagues, take them up and digest them and reduces the number and size of the plaques. IL-33 does so by inducing an enzyme called neprilysin, which is known to degrade soluble amyloid.

In addition, the IL-33 treatment worked by inhibiting the inflammation in the brain tissue, which has been shown earlier to potentiate plaque and tangle formation.
Therefore IL-33 not only helps clear the amyloid plague already formed but also prevent the deposition of the plaques and tangles in the first place.
Professor Liew said, "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.

"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. Nevertheless, this is a good start," Liew said.
The paper, 'IL-33 ameliorates Alzheimer's disease like pathology and cognitive decline' is published today in Proceedings of the National Academy of Sciences USA (PNAS).
Alzheimer's disease is named after Dr Alois Alzheimer who first described it in 1902.

The disease is characterized by progressive memory loss and other cognitive dysfunction such as impaired movement ability, reasoning and judgment. Alzheimer's is a progressive disease that gradually more parts of the brain are damaged and more severe symptoms develop.