Cell type transcriptomics reveal shared genetic mechanisms in Alzheimer's and Parkinson's disease
Bhattacharya, A.; Fon, E. A.; Dagher, A.; Iturria-Medina, Y.; STRATTON, J. A.; Savignac, C.; Stanley, J.; Hodgson, L.; Hammou, B. A.; Bennett, D. A.; Bzdok, D.
Show abstract
Historically, Alzheimers disease (AD) and Parkinsons disease (PD) have been investigated as two distinct disorders of the brain. However, a few similarities in neuropathology and clinical symptoms have been documented over the years. Traditional single gene-centric genetic studies, including GWAS and differential gene expression analyses, have struggled to unravel the molecular links between AD and PD. To address this, we tailor a pattern-learning framework to analyze synchronous gene co-expression at sub-cell-type resolution. Utilizing recently published single-nucleus AD (70,634 nuclei) and PD (340,902 nuclei) datasets from postmortem human brains, we systematically extract and juxtapose disease-critical gene modules. Our findings reveal extensive molecular similarities between AD and PD gene cliques. In neurons, disrupted cytoskeletal dynamics and mitochondrial stress highlight convergence in key processes; glial modules share roles in T-cell activation, myelin synthesis, and synapse pruning. This multi-module sub-cell-type approach offers insights into the molecular basis of shared neuropathology in AD and PD.
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