Single-Cell Comparative Analysis of Early-Stage Alzheimer’s and Parkinson’s Disease-Related Changes in Brain Organoid Models#

Authors#

Sophie Le Bars, Mohamed Soudy, Enrico Glaab

Abstract#

Alzheimer’s disease (AD) and Parkinson’s disease (PD) are complex neurodegenerative disorders with shared biological mechanisms, but their early molecular similarities and differences remain poorly understood. This study aims to elucidate common and divergent changes in cellular processes in the early stages of AD and PD using brain organoid models. We performed a multi-level comparative analysis of single-cell RNA sequencing data from AD and PD brain organoids, integrating gene expression, pathway enrichment, network and cell-cell communication analyses. Our results reveal both common and contrasting changes between AD and PD, including a common dysregulation of apoptotic pathways in astrocytes, a common upregulation of energy metabolism pathways in neurons, and opposing trends in ribosome-related pathways. In particular, we identified the midkine (MDK) signalling pathway as consistently altered across multiple levels of analysis in both diseases. These findings provide new insights into the molecular basis of AD and PD, highlighting potential cross-disease therapeutic targets and disease-specific alterations that may inform tailored treatment strategies for neurodegenerative disorders.