Tau-related Reduction of Glucose Metabolism in Mild Cognitive Impairment Occurs Independently of APOE ε4 Genotype and is Influenced by Aβ

Introduction: Positron emission tomography (PET) imaging studies have shown that amyloid beta (Aβ) is significantly correlated with glucose metabolism in mild cognitive impairment independently of the apolipoprotein E (APOE) ε4 genotype.

Methods: We used a singular value decomposition (SVD) approach to pairwise cross-correlation among tau, Aβ, and fluorodeoxyglucose PET images. The resulting SVD-based tau and Aβ scores as well as the APOE ε4 genotype, were entered as predictors in a voxelwise general linear model for statistical assessment of their effect on FDG.

Results: We found cortical regions where a reduced glucose metabolism was maximally correlated with distributed patterns of tau, accounting for the effect of Aβ and APOE ε4 genotype.

Discussion: By highlighting the more significant role of tau, rather than Aβ, in the reduction of glucose metabolism, our results provide a better understanding of their combined effect in the development and progression of Alzheimer's disease.

Highlights: This study uses a data-driven singular value decomposition approach to the cross-correlation matrix between tau and fluorodeoxyglucose (FDG) images, as well as between FDG and amyloid beta (Aβ) positron emission tomography (PET) images. From a population of mild cognitive impairment subjects, we found that spatially distributed scores of tau PET are associated with an even stronger reduction of glucose metabolism, independent of the apolipoprotein E ε4 genotype and confounded by Aβ. By highlighting the more significant role of tau, rather than Aβ, on the reduction of glucose metabolism, our results provide a better understanding of their combined effects in the development of Alzheimer's disease.