Researchers reveal how a protein interaction can increase Alzheimer’s risk

AD is the most common form of dementia, which affects over 944,000 people in the UK

Researchers from the University of Sheffield’s Institute of Translational Neuroscience (SITraN) and scientists from the UK Dementia Research Institute, Cambridge, have revealed how a protein interaction with a hallmark of Alzheimer’s disease (AD) can increase the risk of developing it.

Published in the journal Nature, the findings from the study open up potential new therapies to treat the neurological condition.

Affecting more than 944,000 people in the UK, dementia is a general term for the impaired ability to think, remember or make decisions on a daily basis.

Currently the most common form of dementia in the UK, AD is caused by a build-up of proteins in the brain, which damage the brain cells’ ability to transmit messages.

Scientists investigated how two fundamental processes in AD are connected: how the inherited apolipoprotein E (APOE) gene is linked with developing the disease by modulating how amyloid-beta accumulates.

Currently the most common risk gene linked to the neurodegenerative disease, APOE has three common forms: APOE2, APOE3 and APOE4, which increases significantly in AD and is carried by two of every five people living with AD.

The team found that all forms of the APOE gene interact with amyloid-beta during its early accumulating stages. However, the high-risk APOE4 variant causes amyloid-beta to become more harmful to neurons, accelerating its build-up compared to other variants of the gene.

“We have identified a specific target: APOE4-Aβ co-aggregates or clumps. By focusing on removing these clumps, we can mitigate the damage Aβ causes to brain cells, enhance the clearance of toxic Aβ, and potentially slow down its accumulation,” explained Dr Suman De, University of Sheffield’s SITraN.

By selectively removing the harmful amyloid clumps that APOE4 interacts with, neuronal loss could be mitigated and the clearance of amyloid from the brain could be accelerated, opening up the potential for new therapies to combat AD.