A Transcriptome and Phenotypic Analyses Between Early and Late Parkinson's Disease to Unravel Disease Mechanisms

Parkinson’s (PD) manifests in patients predominately aged 50 and above although, there are cases with younger patients as early as their 20s. This highlighted the diverse age range impacted by the neurodegenerative disease and underscored the need for a nuanced understanding across the various age groups. For this, a side-by-side comparison was made between early-onset and late-onset PD, using stem cell technology to generate midbrain dopaminergic neurons from patients. The two patients had opposite ages of onset and carried mutations in the same gene, PARK2. Transcriptomic and phenotypic analyses were used to find key signatures that set the two etiologies apart. There, we saw two potential signatures: neurite plasticity and neuroinflammation. The drastic decline of the MAP2 expression was observed in late-onset PD patient neurons compared to the early-onset PD patient neurons. Conversely, there was an enrichment of the upregulated RNAs within the noncanonical NF-B pathway in early-onset PD patient neurons compared to late-onset PD patient neurons. These distinct mechanisms occurring at the cellular level may be among the biological cues signalling the beginning of the neurodegenerative disease at a particular age. Decoding the underlying machinery of PD would further the understanding of the age factor in Parkinson’s and unravel the disease mechanisms.