Transcriptomic similarities in vulnerable and resilient brain regions of Parkinson’s disease and Alzheimer’s disease

Abstract

AbstractBackgroundParkinson’s disease (PD) and Alzheimer’s disease (AD) share multiple pathophysiological features but affect different brain regions. While the hippocampus is highly vulnerable in AD, the loss of dopaminergic neurons in the substantia nigra (SN) is a hallmark of PD. By contrast, other brain regions, such as the cerebellum, seem resilient to neurodegenerative processes in both diseases. However, the biological mechanisms driving brain regional vulnerability and resilience to neurodegeneration in PD and AD remain elusive. Here, we aimed to analyze the transcriptomic profiles of PD and AD in vulnerable (VR) and resilient (RR) brain regions.MethodPD and AD datasets were obtained from the Gene Expression Omnibus public data repository (PD: GSE28894, GSE20186, GSE20314, GSE42966, GSE49036, GSE54282, GSE20164, GSE20163, and GSE8397; AD: GSE118553, GSE44768, GSE036980, GSE084422, GSE1297, GSE29378, and GSE48350). Hippocampal, SN, and cerebellar differential expression analysis was performed to identify differentially expressed genes (DEGs) for each disease versus age‐matched controls. Functional enrichment analysis (FEA) was accomplished to identify similar signatures in VR and RR in PD and AD. Analyses were performed using the R (adj p‐value <0.05).Result607 DEGs overlapped in the VR of PD and AD, while 1780 DEGs in the RR. FEA revealed 114 gene ontology (GO) terms shared between the VR and 276 GO terms overlapping between PD and AD RR. The GO terms were assembled in clusters of biological processes (Table 1). Cluster observation suggests that both VR and RR share similar enriched processes, such as “cellular respiration”, “regulation of neuron death”, “catabolic pathways”, “response to injury and DNA damage”, and “exocytosis and neurotransmitter secretion”. By contrast, “regulation of cell growth”, “response to steroid hormones”, and “regulation of nervous system development” were unique for the RR, while “membrane lipid metabolic process” and “regulation of cell communication” clusters were found only in the VR.ConclusionOur results highlight a transcriptomic landscape shared by PD and AD in both VR and RR. Looking at the similarities between brain regions vulnerable and resilient in different neurodegenerative diseases may contribute to the understanding of their pathogenesis and clinical course, as well as guide the development of therapeutic strategies.