EXPERT REACTION: Different protein clumps for different 'types' of Alzheimer's

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There are subtypes of Alzheimer's disease, and new research suggests each subtype may differ in the structure of the protein clumps that aggregate in patients' brains. International scientists looked at 37 brain tissue samples from 18 individuals, including three subtypes of the disease: typical Alzheimer's, rapidly progressive Alzheimer's, and posterior cortical atrophy Alzheimer's. They found the same patterns of aggregation into fine protein fibres, called fibrils, in two types of the disease, but patients with the rapidly progressive Alzheimer's displayed a range of different fibril structures. The findings could be useful in developing new diagnostic tests for subtypes of Alzheimer's, they say.

Journal/conference: Nature


Funder: The US National Institutes of Health, the UK Medical Research Council and the National Institute of Health Research (NIHR) UCLH/UCL Biomedical Research Centre.

Media Release

From: Springer Nature

Alzheimer’s disease defined by differences in brain deposits

Variations in the structure of amyloid-beta peptide deposits that develop in the brain tissue of patients with Alzheimer's disease are associated with different clinical subtypes of the disease, a study published online in Nature this week indicates. A better understanding of the neurotoxic amyloid-beta aggregates and of correlations between their structure and disease subtypes might help the development of new diagnostic tests and treatments for Alzheimer's disease.

The self-assembly of amyloid-beta peptides into fine protein fibres called fibrils or other structures is a key feature of Alzheimer's disease, and it has been suggested that different fibril formations may be correlated with variations in disease subtypes. To investigate this association, Robert Tycko and colleagues analysed amyloid-beta fibrils prepared from 37 brain tissue samples from 18 individuals. These included patients with either typical Alzheimer's disease or two unusual subtypes — rapidly progressive Alzheimer's disease, in which neurodegeneration occurs within months, and posterior cortical atrophy Alzheimer's disease, which is associated with disruption of visual processing.

The authors find that a single specific fibril structure is dominant in samples from patients with either typical Alzheimer’s disease or the posterior cortical atrophy form, whereas samples from patients with the rapidly progressive disease display a range of different fibril structures. These findings support the theory that different clinical subtypes of Alzheimer's disease might be defined by different amyloid-beta fibril structures.


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Expert Reaction

These comments have been collated by the Science Media Centre to provide a variety of expert perspectives on this issue. Feel free to use these quotes in your stories. Views expressed are the personal opinions of the experts named. They do not represent the views of the SMC or any other organisation unless specifically stated.

Professor Bryce Vissel is Roth Fellow and the Director of the Centre for Neuroscience and Regenerative Medicine at University of Technology, Sydney

Alzheimer’s disease is a devastating condition that is characterised by loss of memory and ultimately more widespread issues and it is ultimately devastating. It is the second leading cause of death in Australia. The toll of this disease on the individuals affected, their families and their carers is substantial; additional to the huge economic burden of this disorder. There are no treatments that can slow or reverse this devastating condition and as a consequence it is urgent that solutions are found to help slow it down.

The cause of Alzheimer’s is largely unknown, and much attention has focused on clumps that are found in the brains of sufferers, called plaques. These plaques are made up of a substance called amyloid-beta peptide. More recently, there has been interest in substances found in the Alzheimer’s brain called amyloid fibrils. The study by Robert Tycko, John Collinge and colleagues, just published in Nature, suggests that variations in the structure of amyloid-beta peptide deposits that develop in the brain tissue of patients with Alzheimer's disease are associated with different clinical subtypes of the disease. The authors show that a single specific structure is dominant in samples from patients with either typical Alzheimer’s disease or the posterior cortical atrophy form, which is associated with disruptions of visual processing, whereas samples from patients with the rapidly progressive disease, in which disease progression occurs within months, display a range of different fibril structures. The findings can be taken to support one hypothesis of Alzheimer's disease: that different clinical subtypes might be associated with different amyloid-beta fibril structures.
However this study does not prove that plaques or amyloid cause Alzheimer’s disease. It is still possible that amyloid is a marker of disease rather than the unique cause. Recent clinical studies that have trialled drugs that remove amyloid have not shown the promise that has been hoped for, although other trials are in progress. For this and a host of other reasons, the role of amyloid fibrils and plaques in causing the disease remains unclear, and currently there are a number of alternative views of what may cause the disorder, including substantial evidence for a role of inflammation. Therefore there are numerous important studies progressing around the world to identify a range of alternative routes to treating this disease. I remain optimistic that a treatment will be found that slows the disease in the foreseeable future.
And it is urgent that cures are found.  There are more than 353,800 Australians living with dementia and 46.8 million worldwide. Without a medical breakthrough, the number of people with dementia in Australia is expected to be almost 900,000 by 2050.

Last updated: 05 Jan 2017 11:38am

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