Amyloid-β and hyperphosphorylated tau synergy drives metabolic decline in preclinical Alzheimer’s disease

• DOI: 10.1038/mp.2016.37
• Publication Date: 2016-03-29T08:08:10Z
• Authors: T A Pascoal; S Mathotaarachchi; S Mohades; A L Benedet; C-O Chung; M Shin; S Wang; T Beaudry; M S Kang; J-P Soucy; A Labbe; S Gauthier; P Rosa-Neto
• Keywords: Standardized uptake value; Posterior cingulate; Amyloid (mycology); Pittsburgh compound B; Tau protein; Cognitive Decline

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 [18F]florbetapir positron emission tomography (PET) cerebrospinal fluid (CSF) measurements at baseline, well [18F]fluorodeoxyglucose ([18F]FDG) PET baseline 24 months. A voxel-based model built associations continuous CSF biomarkers, [18F]FDG standardized uptake value ratios (SUVR). found that synergistic SUVR phosphorylated (p-tau) measurements, rather than sum their independent effects, associated 24-month basal mesial temporal, orbitofrontal, anterior posterior cingulate cortices (P<0.001). In contrast, interactions using amyloid-β1–42 total biomarkers did not associate over time frame The this further support framework hyperphosphorylated aggregates synergistically interact cause downstream AD neurodegeneration. fact, regions displaying reported here were confined brain networks affected early by plaques neurofibrillary tangles. Preventive clinical trials may benefit from combination p-tau enrich populations subjects high probability progression studies, biomarker efficacy.