Novel perspectives on anti-amyloid treatment for the prevention of Alzheimer's disease

July 27, 2017, VIB (the Flanders Institute for Biotechnology)
Diagram of the brain of a person with Alzheimer's Disease. Credit: Wikipedia/public domain.

For decades researches have been investigating the underlying foundations of Alzheimer's disease to provide clues for the design of a successful therapy. This week, VIB/KU Leuven scientists have published breakthrough insights in the prestigious journal Cell. A collaboration between Prof. Lucía Chávez-Gutiérrez and Prof. Bart De Strooper (both VIB-KU Leuven) revealed the molecular basis of the hereditary form of Alzheimer's disease that strikes early in life. These new findings provide powerful insights for the design of novel therapeutic strategies to tackle the disease.The hereditary form of Alzheimer's disease is caused by mutations in the Gamma Secretase enzyme and the APP protein. Gamma Secretase cuts APP several times in a progressive manner, with each cleavage generating a shorter fragment, called amyloid beta, which gets released into the brain.

The VIB-KU Leuven team discovered that disease-causing mutations in Gamma secretase and APP disrupt the cleavage process leading to the generation of longer amyloid beta fragments that are only partially digested. These longer amyloid fragments are thought to cause widespread neuronal death, resulting in memory problems and other symptoms of Alzheimer's disease, before aggregating into (a hallmark of the disease). The researchers uncovered that the disease-causing mutations disrupt this process by weakening the interactions of Gamma Secretase and APP during the progressive cleavages. In that way they promote the premature release of longer amyloid beta fragments. The more the Gamma Secretase-APP interaction is undermined, the sooner Alzheimer's disease develops. The report also suggests that changes in the cellular environment could modulate the interaction between Gamma secretase and APP, and could therefore also affect someone's risk to develop the non-hereditary form of Alzheimer's disease.

These findings have important implications for the prevention or treatment of the disease. Previous attempts to tackle the toxic effects of amyloid beta have mostly focused on blocking its production or removing the amyloid plaques from the brain. However, the new insights suggest that stabilizing the interaction between Gamma secretase and APP might be sufficient to avoid the release of longer and toxic beta fragments and in that way prevent or delay the disease. Prof. Lucía Chávez-Gutiérrez (VIB-KU Leuven): "The mutations causing familial Alzheimer's show the clinical relevance of drugs that strengthen the interaction between Gamma secretase and APP. The more stable the complexes are, the further APP can be processed, resulting in shorter, non-toxic forms of ."

Explore further: Researchers work to block harmful behavior of key Alzheimer's enzyme

Related Stories

Researchers work to block harmful behavior of key Alzheimer's enzyme

February 25, 2016
Enzymes rarely have one job. So, attempts to shut down the enzyme that causes the hallmarks of Alzheimer's disease often mean side effects, because these therapies prevent the enzyme from carrying out many other functions. ...

Road block as a new strategy for the treatment of Alzheimer's

August 22, 2011
Blocking a transport pathway through the brain cells offers new prospects to prevent the development of Alzheimer's. Wim Annaert and colleagues of VIB and K.U. Leuven discovered that two main agents involved in the inception ...

New drugs to find the right target to fight Alzheimer's disease

August 2, 2013
The future is looking good for drugs designed to combat Alzheimer's disease. EPFL scientists have unveiled how two classes of drug compounds currently in clinical trials work to fight the disease. Their research suggests ...

New insight on why people with Down syndrome invariably develop Alzheimer's disease

October 23, 2014
A new study by researchers at Sanford-Burnham Medical Research Institute reveals the process that leads to changes in the brains of individuals with Down syndrome—the same changes that cause dementia in Alzheimer's patients. ...

Recommended for you

Genes linked to Alzheimer's contribute to damage in different ways

June 12, 2018
Multiple genes are implicated in Alzheimer's disease. Some are linked to early-onset Alzheimer's, a condition that develops in one's 30s, 40s and 50s, while others are associated with the more common late-onset form of the ...

Researchers reverse cognitive impairments in mice with dementia

June 8, 2018
Reversing memory deficits and impairments in spatial learning is a major goal in the field of dementia research. A lack of knowledge about cellular pathways critical to the development of dementia, however, has stood in the ...

As mystery deepens over the cause of Alzheimer's, researchers seek new answers

June 6, 2018
For more than 20 years, much of the leading research on Alzheimer's disease has been guided by the "amyloid hypothesis."

Research reveals how Tau aggregates can contribute to cell death in Alzheimer's disease

June 5, 2018
New evidence suggests a mechanism by which progressive accumulation of Tau protein in brain cells may lead to Alzheimer's disease. Scientists studied more than 600 human brains and fruit fly models of Alzheimer's disease ...

How does alcohol influence the development of Alzheimer's disease?

June 4, 2018
Research from the University of Illinois at Chicago has found that some of the genes affected by alcohol and inflammation are also implicated in processes that clear amyloid beta—the protein that forms globs of plaques ...

Dementia patients could remain at home longer thanks to ground breaking technology

June 4, 2018
Innovative new technology will enable people with dementia to receive round the clock observation and live independently in their own homes, a new study in the Journal PLOS One reports.

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.