The Influence of ageing and small genetic variations on Parkinson’s Disease

What is cerebrospinal fluid (CSF) - Interview with Rejko Krüger, neurologist and coordinator of the NCER-PD

For years, a significant challenge in Parkinson’s research has been to disentangle the effects of the disease from the usual ageing process of people living with it. Researchers from the National Center of Excellence in Research on Parkinson’s Disease (NCER-PD) have now made first advancements towards understanding the role of ageing during the disease. A recent study, using extensive data collected from the Luxembourg Parkinson Study, sheds light on how the differences in symptoms that Parkinson’s patients experience can be linked to the ageing process. In the same, study the researcher also explore the effect of the accumulation of many minor genetic variations on the development and progression of the disease. 

Effects of the ageing process on the symptoms of Parkinson’s disease

Researchers and patients have been wondering why people living with Parkinson’s disease for a similar amount of time often show different symptoms and different evolutions of the disease. A significant challenge for research so far has been to disentangle the effect of the disease from the concomitant ageing process, which happens alongside living with the disease. In most cases, Parkinson’s disease is diagnosed after age 60, but there are many exceptions here too.

“Younger patients are often very disheartened after the diagnosis. However, they experience fewer complications of Parkinson’s disease, such as memory disorders, compared to people diagnosed later in life,” explains Dr Lukas Pavelka, researcher at NCER-PD and neurologist in training at CHL. “We now know that the occurrence of certain symptoms is partly due to the ageing process at the time of diagnosis and not to the underlying disease mechanisms.”

Based on the large dataset of the Luxembourg Parkinson Study, in which more than 800 patients and as many healthy people participated, researchers show that especially the difference in so-called ‘non-motor symptoms’, which affect psyche, digestion or sense of smell, is due to the ageing process and not to Parkinson’s disease itself.

The influence of small genetic changes

For a small part of patients, Parkinson’s disease can be attributed to a known heritable genetic mutation. Therefore, researchers have long suspected that a pattern of accumulation of individually insignificant genetic changes could contribute to the disease. Based on the extensive genetic data of participants in the Luxembourg Parkinson Study, researchers have shown that even minor genetic changes can contribute to an earlier onset of the disease.

Since genetic sensitivity to Parkinson’s disease cannot be changed, this may initially sound like bad news. "Our research shows, however, that genetic variations do not impact the progression of Parkinson’s disease or the worsening of symptoms. So this is most likely determined by other factors that we can hopefully influence through a healthier lifestyle, food or future medication,” Dr Pavelka adds. More research is also ongoing to understand how the disease develops from such genetic predispositions and how that process could be avoided altogether. 

You too can help advance research into brain diseases!

Everyone can help drive forward the research on neurodegenerative diseases such as Parkinson’s! If you are older than 50 and are not diagnosed with Parkinson’s or dementia, participate in the Healthy Ageing Study by clicking here. If you cannot participate yourself, share the information about this study with your friends and family so that they can fill out the quick online questionnaire.

Reference: Pavelka, L., Rauschenberger, A., Landoulsi, Z. et al. Age at onset as stratifier in idiopathic Parkinson’s disease – effect of ageing and polygenic risk score on clinical phenotypes.npj Parkinsons Dis. 8, 102 (2022).