In search of an Alzheimer's cure

For decades, the field of Alzheimer's research has been dominated by a major hypothesis: an accumulation of beta-amyloid (amyloid-β) in the brain would be at the origin of Alzheimer's disease. However, despite years of research and billions of dollars spent on clinical trials, there is still no cure.

In an article published in a prestigious newspaper Acta Neuropathologica, researchers at Sydney University of Technology expose evidence to question whether the emphasis on the amyloid hypothesis is preventing the development of alternative – and potentially disruptive – theories in disease research Alzheimer.

"Over the last 30 years, the majority of therapeutic products tested for Alzheimer's disease were aimed at eliminating amyloid-β." Although this strategy is worthwhile, we suggest that the initiation and the Progression of the disease is more complex than can be attributed to amyloid β alone, "says Bryce Vissel, professor of neuroscience and director of the UTS Center for Neuroscience and Regenerative Medicine.

"Alzheimer's disease is a life-changing diagnosis of those living with this disease, their families and friends, and we have written this article to encourage researchers to think outside the box in an attempt to find ways to prevent, stop or reverse the course of the condition. "

New potential research targets remain to be understood. For example, existing research shows that vascular degeneration, neuroinflammation, and synaptic neurodegeneration are present during the progression of Alzheimer's disease, but their role remains unknown.

The researchers also argue that brain pathology is not enough to understand Alzheimer's disease and that a more comprehensive approach to the prediction and diagnosis of the disease is needed – an approach that takes into account the unique characteristics of Alzheimer's disease. each individual.

"Since amyloid-β and the associated pathology are not at all unique to Alzheimer's disease, attempts to construct a mechanism for this condition based solely on it continue, but unsurprisingly, to fail, "says co-author Ian Clark, Professor Emeritus, of the Australian National University.

In addition, the hypothesis of amyloid presents its own challenges: for example, many healthy individuals suffer from β-amyloid without Alzheimer's disease and there are also a significant number of people at which the disease was diagnosed while they did not have amyloid-β. In addition, there are at least nine known and modifiable risk factors for Alzheimer's disease that may not be at all related to amyloid-β deposits.

Alzheimer's disease is the leading cause of dementia, affecting up to 50 million people worldwide and one of the leading causes of death in Australia. The document is important because it provides a balanced counterpoint to an important area of ​​research that could affect our thinking about causes and treatments.

"The understanding of the cause of Alzheimer's disease is incomplete.In this article we have described how the modern perception of Alzheimer's disease has appeared, we have pointed out the gaps in knowledge and suggested new directions for research on Alzheimer's, "says the co-author. Dr. Gary Morris, Postdoctoral Fellow at UTS.

"The most important message to remember is that understanding the normal functioning of the brain and its dysfunctions has developed enormously in recent decades.We propose hypothetical models of the causality of Alzheimer's disease. who need to evolve to adapt to these advances, strategies will probably emerge. "

At the base, Vissel and his team argue for what they see as the next logical step in the global fight against Alzheimer's disease. Their own research focuses on various risk factors and how they work together to cause the disease.

"What is clear is that many clinical trials are failing and solutions are being sought around the world, so we need to start thinking differently and this paper offers some suggestions for doing so," says Vissel.

In this article, we provide important suggestions on how to overcome this disease.

"We are confident that global efforts will lead to a solution."

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More information:
Gary P. Morris et al. Questions about the role of amyloid-β in the definition, etiology and diagnosis of Alzheimer's disease, Acta Neuropathologica (2018). DOI: 10.1007 / s00401-018-1918-8