Local and distant relationships between amyloid, tau and neurodegeneration in Alzheimer's Disease

The relationships between beta-amyloid (A beta), tau and neurodegeneration within Alzheimer's Disease pathogenesis are not fully understood. To explore these associations in vivo, we evaluated 30 A beta PET-positive patients (mean +/- sd age 62.4 +/- 8.3) with mild probable AD and 12 A beta PET-negative healthy controls (HC) (mean +/- sd age 77.3 +/- 6.9) as comparison. All participants underwent 3 T MRI, C-11-PiB (A beta) PET and (18)FA-V1451 (tau) PET. Multimodal correlation analyses were run at both voxel-and region-of-interest levels. C-11-PiB retention in AD showed the most diffuse uptake pattern throughout association neocortex, whereas F-18-AV1451 and gray matter volume reduction (GMR) showed a progressive predilection for posterior cortices (p<0.05 Family-Wise Error-[FWE]-corrected). Voxel-level analysis identified negative correlations between F-18-AV1451 and gray matter peaking in medial and infero-occipital regions (p<0.01 False Discovery Rate-[FDR]-corrected). F-18-AV1451 and C-11-PiB were positively correlated in right parietal and medial/inferior occipital regions (p<0.001 uncorrected). C-11-PiB did not correlate with GMR at the voxel-level. Regionally, F-18-AV1451 was largely associated with local/adjacent GMR whereas frontal C-11-PiB correlated with GMR in posterior regions. These findings suggest that, in mild AD, tau aggregation drives local neurodegeneration, whereas the relationships between A beta and neurodegeneration are not region specific and may be mediated by the interaction between A beta and tau.