DAVRAY, D.; Nilgirwar, P. S.; Jain, S.; Badhe, B.; Shinde, R.; Baranwal, M.

Parkinsons disease (PD) is strongly age -associated, yet how aging reshapes PD[ndash]related transcriptional changes remains unclear. We performed an age[ndash]stratified meta[ndash]analysis of 16 bulk RNA[ndash]seq datasets (646 samples: 314 PD, 332 controls) to distinguish early[ndash]onset (<60 years) from late -onset ([&ge;]60 years) signatures. In the full dataset, 131 significantly (padj <0.05, |log2FC| >1) differentially expressed genes (DEGs) were observed, spanning neuronal activity[ndash]dependent genes (NPAS4, PVALB, ARC, FOSB) and immune/stress-related transcripts (IL3RA, SLC25A6, HSPA1A/B). Age[ndash]specific analyses revealed 31 DEGs in <60, dominated by large[ndash]effect changes in uncharacterized lncRNA LINC02188, pseudogene loci (MUC20P1, RPS28P7), calcium -modulating gene CALML6, lipid-associated gene TLCD3B, and cytoskeletal regulators (TIAM2, KCTD8). In contrast, the [&ge;]60 group showed 181 DEGs enriched for neuronal markers (NPAS4, PVALB) and immune metabolic genes (FGA, NPC1L1, UPK1A, HSPA1A/B). GO/KEGG analyses indicated that the <60 signature centers on actin remodeling, filopodia, axonogenesis, and Rap1 -mediated adhesion/signaling, consistent with early neurite and structural reorganization. The [&ge;]60 signature was enriched for blood microparticles, chemokine activity, infection-related pathways, ER protein processing, and arachidonic/ether lipid and cytokine signaling, pointing to broad immune metabolic and proteostasis dysregulation. Cross[ndash]age comparison showed that classical PD neuronal immediate -early gene changes are largely [&ge;]60 -driven, whereas early-onset PD involves novel lncRNA -calcium-lipid and cytoskeletal modules. These findings highlight LINC02188, TLCD3B and related cytoskeletal/lncRNA genes as novel early -onset PD-associated candidates, and NPC1L1, IL3RA and PVALB as age-amplified markers within the broader PD transcriptomic signature.