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

TitleAmyloid-β and hyperphosphorylated tau synergy drives metabolic decline in preclinical Alzheimer's disease.
Publication TypeJournal Article
Year of Publication2016
AuthorsPascoal TA, Mathotaarachchi S, Mohades S, Benedet AL, Chung C-O, Shin M, Wang S, Beaudry T, Kang MS, Soucy J-P, Labbe A, Gauthier S, Rosa-Neto P
JournalMol Psychiatry
Date Published2016 Mar 29
ISSN1476-5578
Abstract

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<0.001). In contrast, interactions using CSF amyloid-β1-42 and total tau biomarkers did not associate with metabolic decline over a time frame of 24 months. The interaction found in this study further support the framework that amyloid-β and hyperphosphorylated tau aggregates synergistically interact to cause downstream AD neurodegeneration. In fact, the regions displaying the metabolic decline reported here were confined to brain networks affected early by amyloid-β plaques and neurofibrillary tangles. Preventive clinical trials may benefit from using a combination of amyloid-β PET and p-tau biomarkers to enrich study populations of cognitively normal subjects with a high probability of disease progression in studies, using [(18)F]FDG as a biomarker of efficacy.Molecular Psychiatry advance online publication, 29 March 2016; doi:10.1038/mp.2016.37.

DOI10.1038/mp.2016.37
Alternate JournalMol. Psychiatry
PubMed ID27021814

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