Never before seen images of early stage Alzheimer's disease

March 13, 2017

Researchers at Lund University in Sweden have used the MAX IV synchrotron in Lund – the strongest of its kind in the world - to produce images that predate the formation of toxic clumps of beta-amyloid, the protein believed to be at the root of Alzheimer's disease. The unique images appear to contradict a previously unchallenged consensus. Instead of attempting to eliminate beta-amyloid, or so-called plaques, the researchers now suggest stabilizing the protein.

It is a long-held belief in the scientific community that the appear almost instantaneously. Hence the term "popcorn plaques". The infrared spectroscopy images, however, revealed something entirely different.

The researchers could now see structural, molecular changes in the brain.

"No one has used this method to look at Alzheimer's development before. The images tell us that the progression is slower than we thought and that there are steps in the development of Alzheimer's that we know little about. This, of course, sparked our curiosity," says Gunnar Gouras, professor in experimental neurology at Lund University and senior author of the study.

What was happening at this previously unknown phase? Through biochemical identification the first author of the study, Oxana Klementieva, was able to look closer at these early brain changes.

The results revealed another discovery. Namely, that the beta-amyloid did not appear as a single peptide, a widely held belief in the field, but as a unit of four peptides sticking together, a tetramer.

This breakthrough offers a new hypothesis to the cause of the disease. The abnormal separation of these four peptides could be the start of the beta-amyloid aggregation that later turns into plaques.

"This is very, very exciting. In another , transthyretin amyloidosis, the breaking up of the tetramer has been identified as key in disease development. For this disease, there is already a drug in the clinic that stabilizes the tetramers, consequently slowing down disease progression. We hope that stabilizing beta-amyloid in a similar fashion may be the way forward in developing future therapies" says Gunnar Gouras.

The discovery could therefore alter the direction of therapy development for the disease. The aim of most clinical trials today is to eliminate plaques.

Researchers at Lund University will now try to understand the interaction patterns of beta-amyloid preceding the aggregation process. Finding the antidote to whatever breaks the beta-amyloid protein apart could open doors towards a major shift in the of therapies for Alzheimer's disease.

Explore further: 'Pac-Man' gene implicated in Alzheimer's disease

More information: O. Klementieva et al. Pre-plaque conformational changes in Alzheimer's disease-linked Aβ and APP, Nature Communications (2017). DOI: 10.1038/NCOMMS14726

Related Stories

'Pac-Man' gene implicated in Alzheimer's disease

July 26, 2016
A gene that protects the brain from the harmful build-up of amyloid-beta, one of the causative proteins implicated in Alzheimer's disease, has been identified as a new target for therapy by NeuRA researchers.

New findings contradict dominant theory in Alzheimer's disease

October 28, 2011
For decades the amyloid hypothesis has dominated the research field in Alzheimer's disease. The theory describes how an increase in secreted beta-amyloid peptides leads to the formation of plaques, toxic clusters of damaged ...

Alzheimer protein's structure may explain its toxicity

May 7, 2015
Researchers at the University of Illinois at Chicago have determined the molecular structure of one of the proteins in the fine fibers of the brain plaques that are a hallmark of Alzheimer's disease. This molecule, called ...

Hyperactive neurons may be culprit in Alzheimer's

January 13, 2016
A long-term reduction in neuronal activity reduces amyloid plaques associated with Alzheimer's disease, Yale University researchers have found. The study, using mouse models of Alzheimer's, found the opposite is also true—triggering ...

Alzheimer's more versatile than previously known

March 7, 2016
Accumulation of the substance amyloid beta in the brain impairs the memory and cognitive ability in people with Alzheimer's. New findings from Lund University in Sweden show that the cause of amyloid beta pathology might ...

Recommended for you

Dementia with Lewy bodies: Unique genetic profile identified

December 15, 2017
Dementia with Lewy bodies has a unique genetic profile, distinct from those of Alzheimer's disease or Parkinson's disease, according to the first large-scale genetic study of this common type of dementia.

Major cause of dementia discovered

December 11, 2017
An international team of scientists have confirmed the discovery of a major cause of dementia, with important implications for possible treatment and diagnosis.

Canola oil linked to worsened memory and learning ability in Alzheimer's

December 7, 2017
Canola oil is one of the most widely consumed vegetable oils in the world, yet surprisingly little is known about its effects on health. Now, a new study published online December 7 in the journal Scientific Reports by researchers ...

Genetics study suggests that education reduces risk of Alzheimer's disease

December 7, 2017
The theory that education protects against Alzheimer's disease has been given further weight by new research from the University of Cambridge, funded by the European Union. The study is published today in the BMJ.

Healthy mitochondria could stop Alzheimer's

December 6, 2017
Alzheimer's disease is the most common form of dementia and neurodegeneration worldwide. A major hallmark of the disease is the accumulation of toxic plaques in the brain, formed by the abnormal aggregation of a protein called ...

Alzheimer's damage in mice reduced with compound that targets APOE gene

December 6, 2017
People who carry the APOE4 genetic variant face a substantial risk for developing Alzheimer's disease.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.