Brain Imaging and Behavior

, Volume 6, Issue 4, pp 610–620

Beta amyloid, tau, neuroimaging, and cognition: sequence modeling of biomarkers for Alzheimer’s Disease

  • S. Duke Han
  • Jonathan Gruhl
  • Laurel Beckett
  • Hiroko H. Dodge
  • Nikki H. Stricker
  • Sarah Farias
  • Dan Mungas
  • for the Alzheimer’s Disease Neuroimaging Initiative
ADNI: Friday Harbor 2011 Workshop SPECIAL ISSUE


Alzheimer’s disease (AD) is associated with a cascade of pathological events involving formation of amyloid-based neuritic plaques and tau-based neurofibrillary tangles, changes in brain structure and function, and eventually, cognitive impairment and functional disability. The precise sequence of when each of these disease markers becomes abnormal is not yet clearly understood. The present study systematically tested the relationship between classes of biomarkers according to a proposed model of temporal sequence by Jack et al. (Lancet Neurology 9:119–128, 2010). We examined temporal relations among four classes of biomarkers: CSF Aβ, CSF tau, neuroimaging variables (hippocampal volume, ventricular volume, FDG PET), and cognitive variables (memory and executive function). Random effects modeling of longitudinal data obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) was used to test hypotheses that putative earlier markers of AD predicted change in later markers, and that intervening markers reduced effects of earlier on later markers. Specifically, we hypothesized that CSF tau would explain CSF Aβ’s relation to neuroimaging and cognitive variables, and neuroimaging variables would explain tau’s relation to cognitive variables. Consistent with hypotheses, results indicated that CSF Aβ effects on cognition change were substantially attenuated by CSF tau and measures of brain structure and function, and CSF tau effects on cognitive change were attenuated by neuroimaging variables. Contrary to hypotheses, CSF Aβ and CSF tau were observed to have independent effects on neuroimaging and CSF tau had a direct effect on baseline cognition independent of brain structure and function. These results have implications for clarifying the temporal sequence of AD changes and corresponding biomarkers.


Beta amyloid Tau Memory Executive Functions Neuroimaging 


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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • S. Duke Han
    • 1
    • 2
  • Jonathan Gruhl
    • 3
  • Laurel Beckett
    • 4
  • Hiroko H. Dodge
    • 5
  • Nikki H. Stricker
    • 6
    • 7
  • Sarah Farias
    • 8
  • Dan Mungas
    • 8
  • for the Alzheimer’s Disease Neuroimaging Initiative
  1. 1.Department of Behavioral SciencesRush University Medical CenterChicagoUSA
  2. 2.Rush Alzheimer’s Disease CenterRush University Medical CenterChicagoUSA
  3. 3.Department of StatisticsUniversity of WashingtonSeattleUSA
  4. 4.Department of Public Health SciencesUniversity of California DavisDavisUSA
  5. 5.Department of NeurologyOregon Health and Sciences UniversityPortlandUSA
  6. 6.Psychology ServiceVA Boston Healthcare SystemBostonUSA
  7. 7.Department of PsychiatryBoston University School of MedicineBostonUSA
  8. 8.Department of NeurologyUniversity of California DavisDavisUSA

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