Multi-regional alterations in glucose and purine metabolic pathways in the Parkinson’s disease dementia brain

To the authors’ knowledge, this study presents the most comprehensive systematic, semi-targeted metabolomics analysis across multiple regions of the PDD brain, identifying 49 metabolic alterations across nine investigated brain regions, including multiple amino acids as well as metabolites involved in glucose and purine metabolism. The number of alterations varied depending on the brain region investigated, with regions affected earlier in the disease (as described by α-synuclein Braak staging¹⁶) showing a higher number of changes. This suggests that metabolic disruptions reflect the temporal pattern of neuropathology in PDD, rather than the degree of neuronal loss in different regions. One exception to this rule appears to be the CB, which showed a moderate number of metabolite alterations despite traditionally being considered to be relatively unaffected by neurodegeneration in…