Hippocampal metabolic subregions and networks: Behavioral, molecular and pathological aging profiles

peer reviewed ; Introduction: Hippocampal local and network dysfunction is the hallmark of Alzheimer’s disease (AD). Methods: We characterized the spatial patterns of hippocampus differentiation based on brain co-metabolism in healthy older participants and demonstrated their relevance to study local metabolic changes and associated dysfunction in pathological aging. Results: The hippocampus can be differentiated into anterior/posterior and dorsal (CA)/ventral (subiculum) subregions. While anterior and posterior CA show co-metabolism with different regions of the subcortical limbic networks, the anterior and posterior subiculum are parts of cortical networks supporting object-centered memory and higher cognitive demands, respectively. Both networks show relationships with the spatial patterns of gene expression pertaining to cell energy metabolism and AD’s process. Finally, while local metabolism is generally lower in posterior regions, the anterior-posterior imbalance is maximal in late MCI with the anterior subiculum being relatively preserved. Discussion: Future studies should consider bidimensional hippocampal differentiation and in particular the posterior subicular region for better understanding pathological aging.