Cerebral Glucose Hypometabolism in Alzheimer's Disease: A Meta-Analysis and Transcriptomic-Neuroimaging Study.
Level 4 - case-series / case-control
Meta-analysis of observational case-control neuroimaging studies coupled with cross-sectional transcriptomic spatial correlation.
PubMed 42458948 · doi:10.2174/0115672050470646260624045159
What was done
A coordinate-based meta-analysis evaluated 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) data across 17 studies comprising 888 individuals with Alzheimer's disease (AD) and 529 healthy controls. Identified regional metabolic alteration patterns were spatially correlated with post-mortem transcriptomic data from the Allen Human Brain Atlas, followed by pathway enrichment analyses to investigate associated biological functions.
What was found
AD patients showed significant glucose hypometabolism relative to healthy controls across multiple regions: 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, left inferior frontal gyrus (triangular part), and anterior cingulate/paracingulate gyrus. Spatial correlation linked these metabolic deficits to 2,701 genes, which were predominantly enriched for DNA metabolic processes, chromatin remodeling, chromatin/kinase binding, and mitochondrion organization. Specific effect sizes, correlation coefficients, and p-values were not reported in the abstract.
Why it matters
This work synthesizes inconsistent neuroimaging literature to establish a robust spatial map of AD-associated cerebral hypometabolism and links macroscopic metabolic vulnerability to specific microscale genetic pathways, particularly mitochondrial and chromatin regulation.
Limits
The abstract omits quantitative effect sizes, statistical thresholds, and correlation values. Spatial transcriptomics relied on the Allen Human Brain Atlas, which reflects gene expression in non-diseased adult brains rather than AD-affected brain tissue. The coordinate-based meta-analytic design cannot adjust for underlying heterogeneity in patient disease staging, diagnostic criteria, or PET acquisition protocols across the included studies.
Cited by
- supports In Alzheimer's disease, the brain's capacity to metabolize and utilize glucose declines.