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.