A study of a rare case early-onset Parkinson’s disease has revealed molecular changes in platelets, suggesting the potential of the blood’s smallest component in indicating a progression of the neurodegenerative disorder.
The study, published in the journal Movement Disorders, describes a patient in Spain with early-onset Parkinson’s disease and rapid progression to dementia, carrying a triplication of a genomic region containing ‘SNCA’, the gene responsible for producing alpha-synuclein, that clumps in Parkinson’s disease.
Researchers, including those from the Germans Trias i Pujol Research Institute in Spain, said that the SNCA alteration arose de novo, meaning it was not inherited from either parent.
By tracking the patient over time, the team compared gene expression — which provides information about gene activity — at age 41, during the early stages of the disease, at the age of 44, after dementia developed.
They observed more progression-associated changes in gene expression in platelets than in whole blood.
“Longitudinally, PLTs (platelets) showed substantially more progression-related transcriptional changes than blood, indicating higher capacity to discriminate disease stages,” the authors wrote.
Genes, whose expression changed as part of Parkinson’s progression, included those involved in mitochondrial function, protein synthesis and the regulation of inflammation.
The findings offer insights into molecular processes that could be involved in disease progression, the researchers said.
“This exceptional case has allowed us to study how molecular signals evolve as Parkinson’s disease progresses. Platelets show more pronounced changes than whole blood, highlighting their value as an accessible source for investigating potential biomarkers of progression,” first author Susanna Jiménez-Román, a predoctoral researcher from the Germans Trias i Pujol Research Institute, said.
The team also analysed selected genes in an independent cohort of 15 patients with early-onset sporadic Parkinson’s disease and 18 healthy individuals to explore whether similar changes occurred in other forms of the disease.
The patients’ platelets revealed differences in expression that matched some of the changes found in the rare genetic case, including reduced expression of an SNCA RNA variant and two genes involved in protein synthesis. However, no significant differences were observed in whole blood for the genes examined.
The overlap points to possible shared molecular mechanisms between genetic and sporadic forms of the disease, the researchers said.
“The relevance of this study extends beyond this rare genetic alteration. Some of the molecular signals identified are also present in patients with early-onset sporadic Parkinson’s disease. This suggests that studying rare cases can help us understand shared mechanisms and open up new avenues for investigating disease progression,” says Jiménez.
(PTI)
