Beta amyloid, tau, neuroimaging, and cognition: Sequence modeling of biomarkers for Alzheimer's Disease

S. Duke Han, Jonathan Gruhl, Laurel A Beckett, Hiroko H. Dodge, Nikki H. Stricker, Sarah E Tomaszewski Farias, Dan M Mungas

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)610-620
Number of pages11
JournalBrain Imaging and Behavior
Volume6
Issue number4
DOIs
StatePublished - 2012

Fingerprint

Amyloid
Neuroimaging
Cognition
Alzheimer Disease
Biomarkers
Brain
Neurofibrillary Tangles
Executive Function
Amyloid Plaques
Neurology

Keywords

  • Beta amyloid
  • Executive Functions
  • Memory
  • Neuroimaging
  • Tau

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health
  • Neurology
  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience
  • Behavioral Neuroscience
  • Radiology Nuclear Medicine and imaging

Cite this

Beta amyloid, tau, neuroimaging, and cognition : Sequence modeling of biomarkers for Alzheimer's Disease. / Han, S. Duke; Gruhl, Jonathan; Beckett, Laurel A; Dodge, Hiroko H.; Stricker, Nikki H.; Tomaszewski Farias, Sarah E; Mungas, Dan M.

In: Brain Imaging and Behavior, Vol. 6, No. 4, 2012, p. 610-620.

Research output: Contribution to journalArticle

@article{92ff35db92ea4edcb9eb9a1974cdc116,
title = "Beta amyloid, tau, neuroimaging, and cognition: Sequence modeling of biomarkers for Alzheimer's Disease",
abstract = "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.",
keywords = "Beta amyloid, Executive Functions, Memory, Neuroimaging, Tau",
author = "Han, {S. Duke} and Jonathan Gruhl and Beckett, {Laurel A} and Dodge, {Hiroko H.} and Stricker, {Nikki H.} and {Tomaszewski Farias}, {Sarah E} and Mungas, {Dan M}",
year = "2012",
doi = "10.1007/s11682-012-9177-0",
language = "English (US)",
volume = "6",
pages = "610--620",
journal = "Brain Imaging and Behavior",
issn = "1931-7557",
publisher = "Springer New York",
number = "4",

}

TY - JOUR

T1 - Beta amyloid, tau, neuroimaging, and cognition

T2 - Sequence modeling of biomarkers for Alzheimer's Disease

AU - Han, S. Duke

AU - Gruhl, Jonathan

AU - Beckett, Laurel A

AU - Dodge, Hiroko H.

AU - Stricker, Nikki H.

AU - Tomaszewski Farias, Sarah E

AU - Mungas, Dan M

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

KW - Beta amyloid

KW - Executive Functions

KW - Memory

KW - Neuroimaging

KW - Tau

UR - http://www.scopus.com/inward/record.url?scp=84871719595&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84871719595&partnerID=8YFLogxK

U2 - 10.1007/s11682-012-9177-0

DO - 10.1007/s11682-012-9177-0

M3 - Article

C2 - 22648764

AN - SCOPUS:84871719595

VL - 6

SP - 610

EP - 620

JO - Brain Imaging and Behavior

JF - Brain Imaging and Behavior

SN - 1931-7557

IS - 4

ER -