500 ROS/MAP participants were included in this analysis. For each
participant, data was available on cognitive assessments during lifetime,
postmortem AD brain pathology, and brain metabolic profiles from the
dorsolateral prefrontal cortex (DLPFC) region. Metabolic profiles were
investigated for associations with AD-related traits and a metabolite
interaction network was inferred using a Gaussian graphical model (GGM).
Associations were tested for replication in 83 temporal cortex samples from the
Mayo Clinic brain bank cohort and compared to a previously published brain-based
study. Finally, various pathways previously implicated in AD were metabolically
characterized, and a detailed metabolomic/proteomic characterization of the
glutamate/GABA neurotransmitter pathway was generated.