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 [F-18]FDG-PET images, as well as of significant hypometabolism in patients compared to healthy controls. Neurogranin- and alpha-synuclein-VOIs included left precuneus and/or posterior cingulate cortex (PC and/or PCC) and partially overlapped hypometabolism at those sites. beta-synuclein- and neurofilament light chain (NfL)-VOIs regarded either left or right lateral temporal areas, respectively, with partial overlap with hypometabolism only for the beta-synuclein-VOI, whereas the NfL-VOI did not include hypometabolic regions. We speculate that CSF neurogranin and alpha-synuclein express an already established hippocampal damage leading to PC and/or PCC deafferentation and hypometabolism. beta-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. (C) 2022 Elsevier Inc. All rights reserved.