Distinct metabolic signatures of Alzheimer's and Parkinson's disease revealed through genetic overlap with metabolic markers
Stinson, S. E.; Shadrin, A. A.; Rahman, Z.; Rodevand, L.; Broce, I. J.; Persson, K.; Selbaek, G.; Stefansson, H.; Haavik, J.; Parker, N.; Koch, E.; Frei, O.; O'Connell, K. S.; Smeland, O. B.; Djurovic, S.; Dale, A. M.; van der Meer, D.; Andreassen, O. A.
Show abstract
Metabolic dysfunction is increasingly implicated in neurodegenerative diseases, yet the genetic architecture linking metabolic markers with Alzheimers disease (AD) and Parkinsons disease (PD) remains unclear. We systematically analysed phenotypic and genetic relationships between 249 circulating metabolites with AD and PD, comparing patterns to body mass index (BMI), type 2 diabetes (T2D), coronary artery disease (CAD) and stroke. Using linkage disequilibrium score regression and bivariate Gaussian mixture modeling, we identified distinct genetic overlap. AD correlated positively with cardiometabolic traits (BMI, rs=0.11; T2D, rs=0.23; CAD, rs=0.22; stroke, rs=0.18), whereas PD showed opposing patterns (AD-PD rs=-0.36). Mendelian randomization identified bi-directional causal effects of lipid measures on AD and divergent effects of glutamine on AD and PD. Conjunctional FDR analyses mapped 1,377 shared genes, implicating lipid metabolism in AD and synaptic processes in PD. These findings disentangle disease-specific pathways and inform therapeutic strategies targeting metabolic health.
Matching journals
The top 8 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- A public resource of single cell transcriptomes and multiscale networks from persons with and without Alzheimer's disease 97%
- Individual bioenergetic capacity as a potential source of resilience to Alzheimer’s disease 96%
- Cell-type-specific Alzheimer’s disease polygenic risk scores are associated with distinct disease processes in Alzheimer’s disease 96%
Similar papers in this journal
- Interaction of sortilin with apolipoprotein E3 enables neurons to use long-chain fatty acids as alternative metabolic fuel 93%
- Mitochondrial complex III-derived ROS amplify immunometabolic changes in astrocytes and promote dementia pathology 92%
- Genome-microbiome interplay provides insight into the determinants of the human blood metabolome 92%
Similar papers in this journal
- APOE4 Lowers Energy Expenditure and Impairs Glucose Oxidation by Increasing Flux through Aerobic Glycolysis 95%
- Identification of a specific APOE transcript and functional elements associated with Alzheimer's disease 95%
- 17q21.31 sub-haplotypes underlying H1-associated risk for Parkinsons disease are associated with LRRC37A/2 expression in astrocytes 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.