Exploring the brain metabolic correlates of process-specific CSF biomarkers in patients with MCI due to Alzheimer's disease: preliminary data

We explored the brain metabolism correlates of emergent cerebrospinal fluid (CSF) biomarkers in a group of 26 patients with prodromal Alzheimer's disease (AD). Distinct volumes of interest (VOIs) expressed the sites of correlation between CSF biomarkers and brain metabolism as determined on [18F]FDG-PET images, as well as of significant hypometabolism in patients compared to healthy controls. Neurogranin- and α-synuclein-VOIs included left precuneus and/or posterior cingulate cortex (PC and/or PCC) and partially overlapped hypometabolism at those sites. β-synuclein- and neurofilament light chain (NfL)-VOIs regarded either left or right lateral temporal areas, respectively, with partial overlap with hypometabolism only for the β-synuclein-VOI, whereas the NfL-VOI did not include hypometabolic regions. We speculate that CSF neurogranin and α-synuclein express an already established hippocampal damage leading to PC and/or PCC deafferentation and hypometabolism. β-synuclein may represent the progression of synaptopathy in the temporal lobe, while NfL the axonal injury in right temporal regions where neuronal loss is not yet evident.