Impact of tau and amyloid burden on glucose metabolism in Alzheimer's disease

Abstract

In a multimodal PET imaging approach, we determined the differential contribution of neurofibrillary tangles (measured with [¹⁸F]AV-1451) and beta-amyloid burden (measured with [¹¹C]PiB) on degree of neurodegeneration (i.e., glucose metabolism measured with [¹⁸F]FDG-PET) in patients with Alzheimer's disease. Across brain regions, we observed an interactive effect of beta-amyloid burden and tau deposition on glucose metabolism which was most pronounced in the parietal lobe. Elevated beta-amyloid burden was associated with a stronger influence of tau accumulation on glucose metabolism. Our data provide the first in vivo insights into the differential contribution of Aβ and tau to neurodegeneration in Alzheimer's disease.

Figure 1

Spatial correspondence of mean Fluordexoglucose (FDG) deviation and mean tau deviation but not amyloid deviation in AD patients. AD, Alzheimer's disease patients. Deviation images were projected on the lateral surface of the left and the right hemisphere using FreeSurfer.

Figure 2

(A) Significant relationship of the pattern of FDG hypometabolism and the pattern of tau deposition across brain regions in cortical and subcortical AAL regions. (B) A positive relationship of the pattern of FDG hypometabolism and the pattern of Aβ burden in cortical and subcortical AAL regions. (C) Regression plane of the interaction of tau (y‐axis) and Aβ (x‐axis) deposition on hypometabolism (z‐axis). AAL, automated anatomical labeling.