Are Parkinson's and Alzheimer's Linked?

The human body is incredibly complex, which makes it all the more exciting when scientists unravel a new mystery. The latest theory to emerge is an underlying link between Parkinson’s and Alzheimer’s, two of the world’s most common neurodegenerative diseases. Despite their considerable differences, researchers are maintaining that both have a shared biochemical origin. In other words, they appear to be triggered by the same enzyme.

Known as AEP, asparagine endopeptidase is a lysosomal cysteine proteinase that’s activated during the ageing process. In cases of Alzheimer's, AEP proteolytically degrades the Tau proteins that exist inside brain cells. They then clump and tangle, which breaks down microtubule assembly function and fast-tracks neurodegeneration. For Parkinson's, AEP appears to aggregate alpha-synuclein proteins. They then form deposits known as Lewy bodies, which develop inside nerve cells and can impact movement, behaviour and mood.

AEP leaves a trail of destruction

While the two diseases are very different, Dr Keqiang Ye of Emory University is spearheading the theory that AEP contributes to both protein aggregations. The milestone findings offer exciting new insight into both diseases, and could help advance treatments for both Parkinson's and Alzheimer's.

The research was published in the journal Nature Structural and Molecular Biology, with Ye explaining that "In Parkinson's, alpha-synuclein behaves much like Tau in Alzheimer's.” He goes on to reason that when AEP cuts Tau, it's highly likely that it will also cut alpha-synuclein. Ye successfully confirmed the theory when he created an antibody that recognises cleaved alpha-synuclein, but not the uncut molecule. It was then used it to check whether cutting had occurred in cells.

Using AEP inhibitors to protect brain proteins

With this in mind, Ye and his team have put forward the radical new idea of using AEP inhibitors to reduce the risk of both Alzheimer's and Parkinson's. Such inhibitors have already been used in animal trials, with Ye and his team planning to continue to explore the link.

The findings are positive, though Ye was quick to caution that there’s probably far more to the story than simply AEP. Both Alzheimer's and Parkinson's are incredibly complex diseases, and there’s still a vast amount of ground to cover before the theory makes it to human trials.

Now celebrating its tenth year of research and innovation, Diamond Light Source is the UK’s leading synchrotron radiation facility. It plays an important role in homegrown research, including studies relating to Parkinson’s and Alzheimer’s. For more information on its two new wings, ‘Adding Electrons to Synchrotron Imaging Synergies’ spotlights the latest findings from the electron Physical Sciences Imaging Centre (ePSIC) and the electron Bio-Imaging Centre (eBIC).