Amyloid-[beta] and hyperphosphorylated tau synergy drives metabolic decline in preclinical Alzheimer's disease

This study was designed to test the interaction between amyloid-β and tau proteins as a determinant of metabolic decline in preclinical Alzheimer's disease (AD). We assessed 120 cognitively normal individuals with [18 F]florbetapir positron emission tomography (PET) and cerebrospinal fluid (CSF) measurements at baseline, as well as [18 F]fluorodeoxyglucose ([18 F]FDG) PET at baseline and at 24 months. A voxel-based interaction model was built to test the associations between continuous measurements of CSF biomarkers, [18 F]florbetapir and [18 F]FDG standardized uptake value ratios (SUVR). We found that the synergistic interaction between [18 F]florbetapir SUVR and CSF phosphorylated tau (p-tau) measurements, rather than the sum of their independent effects, was associated with a 24-month metabolic decline in basal and mesial temporal, orbitofrontal, and anterior and posterior cingulate cortices (P