Cerebral Glucose Hypometabolism in Alzheimer’s Disease: A Meta-Analysis and Transcriptomic-Neuroimaging Study

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Introduction: Cerebral glucose hypometabolism is known to occur in Alzheimer’s Disease (AD). However, the spatial pattern of these metabolic alterations remains inconsistent across studies, and the molecular mechanisms linking regional metabolic vulnerability to gene expression profiles are poorly understood, thus highlighting the neuroimaging–transcriptomics gap. Methods: We performed a coordinate-based meta-analysis of 18F-fluorodeoxyglucose positron emission tomography data from 17 studies. This involved 888 AD individuals and 529 healthy controls. Spatial correlation analysis of metabolic alterations and transcriptomic gene data from the Allen Human Brain Atlas was performed. Enrichment analysis was conducted to explore biological processes associated with the identified genes. results: Compared with healthy controls, AD patients showed significant glucose hypometabolism in regions including the bilateral precuneus, median cingulate / paracingulate gyri, posterior cingulate gyri, angular gyri, inferior parietal gyri, supramarginal gyri, middle occipital gyri, middle temporal gyri, inferior temporal gyri, the left inferior frontal gyrus (triangular part) and anterior cingulate / paracingulate gyrus. Moreover, spatial correlation analysis revealed that these changes were associated with 2701 genes, which were enriched for AD-relevant biological processes such as DNA metabolic process, chromatin remodeling, chromatin/kinase binding, inorganic ion transmembrane transport, and mitochondrion organization. Results: Compared with healthy controls, AD patients showed significant glucose hypometabolism in regions including the bilateral precuneus, median cingulate/paracingulate gyri, posterior cingulate gyri, angular gyri, inferior parietal gyri, supramarginal gyri, middle occipital gyri, middle temporal gyri, inferior temporal gyri, the left inferior frontal gyrus (triangular part), and anterior cingulate/ paracingulate gyrus. Spatial correlation analysis revealed that these changes were correlated with 2,701 genes. The identified genes were mainly involved in biological processes such as the DNA metabolic process, chromatin remodeling, chromatin/kinase binding, and mitochondrion organization. Discussion: The meta-analysis and transcriptomic-neuroimaging study revealed consistent patterns of brain metabolism and AD-associated gene sets. We also identified related biological processes. These results link microscale gene expression to macroscale glucose hypometabolism and offer new mechanism perspectives. Conclusion: This study maps AD-related glucose hypometabolism to specific transcriptional profiles, providing novel insights into the molecular basis of metabolic alterations in AD.

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