Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) share a common biological feature: the abnormal accumulation of a protein called alpha-synuclein inside nerve cells. These proteins clump together in small structures called Lewy bodies – structures that give their name to DLB. In a new study published in the Journal of Clinical Investigation, a team of US-based researchers identify a very early hallmark of Lewy body diseases, which can be detected using PET scans of the heart. Many researchers now believe that the biological processes that drive Alzheimer’s disease start many years before symptoms become apparent. The same is thought to be true of other neurodegenerative diseases like PD and DLB: scientists have shown that neurodegeneration – driven by the accumulation of abnormal proteins in nerve cells – starts many years before motor or cognitive symptoms occur.
Aiming to find new ways to detect the very early stages of Lewy body diseases, researchers at the US National Institutes of Health analysed data from PDRisk, a prospective, longitudinal study in which 82 individuals at risk for Lewy body diseases (determined by genetic risk factors, olfactory and sleep issues, and orthostatic hypotension) underwent long-term followup. Their analysis focused on 34 at-risk individuals who were followed for up to 7.5 years, undergoing regular clinical examinations as well as MRI and PET scans. The PET scans measured the uptake of a protein called dopamine, which is negatively affected in Lewy body diseases. Rather than focusing entirely on the brain, researchers also studied PET scans of the heart, to understand whether altered dopamine uptake can predict the development of PD or DLB in later years.
These analyses found that those who had low levels of 18F-dopamine in the heart were much more likely to develop PD or DLB: eight of nine people were later diagnosed with one of these diseases. Conversely, of the 25 participants with normal levels of dopamine uptake in the heart, only one of the 11 who completed 7 years of follow-up went on to develop a Lewy body disease. The researchers concluded that Cardiac 18F-dopamine PET can efficiently distinguishes at-risk individuals who are diagnosed subsequently with a Lewy body disease, from those who are not.