title: Synergistic interaction between amyloid and tau predicts the progression to dementia.
abstract: BACKGROUND
  Recent literature proposes that amyloid β (Aβ) and phosphorylated tau (p-tau) synergism accelerates biomarker abnormalities in controls. Yet, it remains to be answered whether this synergism is the driving force behind Alzheimer disease (AD) dementia.
  
  
  METHODS
  We stratified 314 mild cognitive impairment individuals using [18F]florbetapir positron emission tomography Aβ imaging and cerebrospinal fluid p-tau. Regression and voxel-based logistic regression models with interaction terms evaluated 2-year changes in cognition and clinical status as a function of baseline biomarkers.
  
  
  RESULTS
  We found that the synergism between [18F]florbetapir and p-tau, rather than their additive effects, was associated with the cognitive decline and progression to AD. Furthermore, voxel-based analysis revealed that temporal and inferior parietal were the regions where the synergism determined an increased likelihood of developing AD.
  
  
  CONCLUSIONS
  Together, the present results support that progression to AD dementia is driven by the synergistic rather than a mere additive effect between Aβ and p-tau proteins.
authors.affiliation: Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, Montreal, Canada.
authors.forename: Tharick A
authors.initials: TA
authors.lastname: Pascoal
authors.affiliation: Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, Montreal, Canada.
authors.forename: Sulantha
authors.initials: S
authors.lastname: Mathotaarachchi
authors.affiliation: Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, Montreal, Canada.
authors.forename: Monica
authors.initials: M
authors.lastname: Shin
authors.affiliation: Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, Montreal, Canada; CAPES Foundation, Ministry of Education of Brazil, Brasília, Brazil.
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Benedet
authors.affiliation: Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, Montreal, Canada.
authors.forename: Sara
authors.initials: S
authors.lastname: Mohades
authors.affiliation: Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, Montreal, Canada.
authors.forename: Seqian
authors.initials: S
authors.lastname: Wang
authors.affiliation: Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, Montreal, Canada.
authors.forename: Tom
authors.initials: T
authors.lastname: Beaudry
authors.affiliation: Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, Montreal, Canada.
authors.forename: Min Su
authors.initials: MS
authors.lastname: Kang
authors.affiliation: Montreal Neurological Institute, Montreal, Canada.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Soucy
authors.affiliation: Douglas Hospital Research Centre, McGill University, Montreal, Canada; Department of Epidemiology, Biostatistics & Occupational Health, McGill University, Montreal, Canada.
authors.forename: Aurelie
authors.initials: A
authors.lastname: Labbe
authors.affiliation: AD Research Unit, The McGill University Research Centre for Studies in Aging, Montreal, Canada; McGill University, Montreal, Canada.
authors.forename: Serge
authors.initials: S
authors.lastname: Gauthier
authors.affiliation: Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, Montreal, Canada; Montreal Neurological Institute, Montreal, Canada; AD Research Unit, The McGill University Research Centre for Studies in Aging, Montreal, Canada; McGill University, Montreal, Canada; Department of Neurology and Neurosurgery, McGill University, Montreal, Canada. Electronic address: pedro.rosa@mcgill.ca.
authors.forename: Pedro
authors.initials: P
authors.lastname: Rosa-Neto
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000235:genetics / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000814:Aniline Compounds; D053327:Apolipoprotein E4 / Q000235:genetics; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D005026:Ethylene Glycols; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016015:Logistic Models; D008297:Male; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D053327:Apolipoprotein E4; D015415:Biomarkers; D005026:Ethylene Glycols; C054369:MAPT protein, human; D019275:Radiopharmaceuticals; D016875:tau Proteins; C545186:florbetapir
keywords: Alzheimer disease; Amyloid-PET; Mild cognitive impairment; Neuropsychological tests; Phosphorylated tau