Synergistic interaction between amyloid and tau predicts the progression to dementia

Alzheimers Dement. 2017 Jun;13(6):644-653. doi: 10.1016/j.jalz.2016.11.005. Epub 2016 Dec 23.


Introduction: 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.

Discussion: 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.

Keywords: Alzheimer disease; Amyloid-PET; Mild cognitive impairment; Neuropsychological tests; Phosphorylated tau.

MeSH terms

  • Aged
  • Alzheimer Disease / diagnostic imaging*
  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism*
  • Amyloid beta-Peptides / metabolism*
  • Aniline Compounds
  • Apolipoprotein E4 / genetics
  • Biomarkers / metabolism
  • Brain / diagnostic imaging*
  • Brain / metabolism*
  • Cognitive Dysfunction / diagnostic imaging
  • Cognitive Dysfunction / genetics
  • Cognitive Dysfunction / metabolism
  • Disease Progression
  • Ethylene Glycols
  • Female
  • Follow-Up Studies
  • Humans
  • Logistic Models
  • Male
  • Neuropsychological Tests
  • Positron-Emission Tomography
  • Radiopharmaceuticals
  • tau Proteins / cerebrospinal fluid*


  • Amyloid beta-Peptides
  • Aniline Compounds
  • Apolipoprotein E4
  • Biomarkers
  • Ethylene Glycols
  • MAPT protein, human
  • Radiopharmaceuticals
  • tau Proteins
  • florbetapir