A team of researchers from King’s College London (UK) have uncovered the earliest signs of Parkinson’s disease (PD) in the brain, many years before patients demonstrate any symptoms.
The results, which have been published in The Lancet Neurology, challenge the traditional view of the disease and could potentially lead to screening tools for identifying people at greatest risk.
This new study provides the first evidence of a central role for serotonin in the very earliest stages of Parkinson’s and suggests that changes to the serotonin system could act as a key early warning signal for the disease.
Chief investigator, Marios Politis (King’s College London), commented: “PD has traditionally been thought of as occurring due to damage in the dopamine system, but we show that changes to the serotonin system come first, occurring many years before patients begin to show symptoms.”
“Our results suggest that early detection of changes in the serotonin system could open doors to the development of new therapies to slow, and ultimately prevent, progression of PD.”
Investigators recruited 14 participants with the SNCA gene mutation and compared them with 65 participants with non-genetic PD and 25 healthy volunteers. The team found that the serotonin system starts to malfunction in people with Parkinson’s well before symptoms affecting movement occur, and before the first changes in the dopamine system are observed.
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Heather Wilson (King’s College London), first author of the study, explained: “We found that serotonin function was an excellent marker for how advanced PD has become. Crucially, we found detectable changes to the serotonin system among patients who were not yet diagnosed. Therefore, brain imaging of the serotonin system could become a valuable tool to detect individuals at risk for PD, monitor their progression and help with the development of new treatments.”
Within their study, the researchers concluded that: “Future work might establish whether serotonin transporter imaging is suitable as an adjunctive tool for screening and monitoring progression for individuals at risk or patients with PD to complement dopaminergic imaging, or as a marker of Parkinson’s burden in clinical trials.”
Sources: Wilson H, Dervenoulas G, Pagano G et al. Serotonergic pathology and disease burden in the premotor and motor phase of A53T a-synuclein parkinsonism: a cross-sectional study. Lancet Neurol. doi:10.1016/S1474/4422(19)30140-1 (2019) (Epub ahead of print); King’s College London. Study reveals roots of Parkinson’s in the brain. Press release: www.kcl.ac.uk/home