Daily Archives: July 12, 2018

New Hope To Fight Alzheimer’s

It is known that the onset of Alzheimer’s disease (AD) is associated with the accumulation of Amyloid beta () peptides in small molecular clusters known as oligomers. These trigger the formation of so-called ‘neurofibrillary tangles’ within neurons hamper their workings, ultimately causing cell death and so significant cognitive decline. Very large Aβ oligomers which form plaques outside neurons, alongside neuroinflammation have also been found to play a key part in the progression of the disease.


The EU-funded iRhom2 in AD project took as its starting point the protein iRhom2, which has been identified as a genetic risk factor for AD due to its pro-inflammatory properties. The team were able to explore further the influence of iRhom2 on neuroinflammation in mice. iRhom2 recently emerged as a protein of note in AD as it aids the maturation of an enzyme called TACE (tumor necrosis factor-α converting enzyme) guiding it towards a cell’s plasma membrane where the enzyme releases a cell-signalling cytokine (TNFα), implicated in the regulation of inflammatory processes. While mice studies have shown that TNFα-dependent inflammation can lead to sepsis and rheumatoid arthritis, it is also thought that the process contributes to neuroinflammatory signalling events, which can cause harm in the brain.

The EU-funded iRhom2 in AD project worked with mice that are prone to develop the hallmarks of AD, amyloid plaques and memory deficits. The team genetically altered iRhom2 in the mice then analysed the progression of the pathology using an array of biochemical and histological methods, together with a number of behavioural tests to assess cognitive decline. The results were somewhat surprising.

We initially hypothesised that iRhom2 would affect one specific aspect of neuroinflammation in AD. What we discovered was even more exciting as it actually affects several different aspects of neuroinflammation simultaneously. So modulating iRhom2 appears particularly well suited to interfere with AD,” explains project coordinator Prof. Dr. Stefan Lichtenthaler.

Source: https://cordis.europa.eu/