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

Background Parkinson’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. Method PD 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