By assessing the large-scale, cross-correlation between tau and FDG PET images with the SVD approach, our analysis revealed several key findings, including:
- Reduction of glucose metabolism is not associated with APOE ε4 genotype
- Spatially distributed tau has a much greater role in the reduction of glucose metabolism than β-amyloid
- Tau-related reduction of glucose metabolism was pronounced even after adjustment for β-amyloid
- A gradual increase in β-amyloid continuously modulates the tau-related reduction in glucose metabolism
- Local tau in initial seeding regions had a prominent role the reduction of glucose levels in remote neocortical regions
By highlighting the more significant role of spatially distributed tau scores, rather than β-amyloid, in the reduction of glucose metabolism, this work could have important consequences in the therapeutic treatment of Alzheimer's disease, stressing the importance of tau-related pathology in the early stages of the disease.
We have explored whole brain associations between glucose metabolism, tau, and APOE ε4 genotype in a sample of MCI subjects from the ADNI study. Our analysis also assesses the impact of β-amyloid on the spatial relationship between glucose metabolism and tau.
To our knowledge, this study is the first to relate glucose metabolism with tau and β-amyloid from a whole brain network perspective that accounts for distributed-to-distributed and local-to-distributed patterns of cross-correlation.