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

In landmark study, doctors say test identifies people most likely to get Alzheimer's

September 24, 2018
The beginning was the worst. It frustrated Janet Parkerson when her father started to forget what he had done that day or the day before.

Study clarifies ApoE4's role in dementia

September 20, 2018
ApoE4, a protein linked to both Alzheimer's disease and a form of dementia caused by damage of blood vessels in the brain, increases the risk of cognitive impairment by reducing the number and responsiveness of blood vessels ...

Machine learning IDs markers to help predict Alzheimer's

September 19, 2018
Nearly 50 million people worldwide have Alzheimer's disease or another form of dementia. These irreversible brain disorders slowly cause memory loss and destroy thinking skills, eventually to such an extent that self-care ...

Discovery could explain failed clinical trials for Alzheimer's, and provide a solution

September 19, 2018
Researchers at King's College London have discovered a vicious feedback loop underlying brain degeneration in Alzheimer's disease which may explain why so many drug trials have failed. The study also identifies a clinically ...

Air pollution may be linked to heightened dementia risk

September 18, 2018
Air pollution may be linked to a heightened risk of developing dementia, finds a London-based observational study, published in the online journal BMJ Open. The associations found couldn't be explained by factors known to ...

A new approach for finding Alzheimer's treatments

September 11, 2018
Considering what little progress has been made finding drugs to treat Alzheimer's disease, Maikel Rheinstädter decided to come at the problem from a totally different angle—perhaps the solution lay not with the peptide ...

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.