Plasma Tau Association with Brain Atrophy in Mild Cognitive Impairment and Alzheimer's Disease

for the Alzheimer Disease Neuroimaging Initiative

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Background: Peripheral (plasma) and central (cerebrospinal fluid, CSF) measures of tau are higher in Alzheimer's disease (AD) relative to prodromal stages and controls. While elevated CSF tau concentrations have been shown to be associated with lower grey matter density (GMD) in AD-specific regions, this correlation has yet to be examined for plasma in a large study. Objective: Determine the neuroanatomical correlates of plasma tau using voxel-based analysis. Methods: Cross-sectional data for 508 ADNI participants were collected for clinical, plasma total-tau (t-tau), CSF amyloid (Aβ42) and tau, and MRI variables. The relationship between plasma tau and GMD and between CSF t-tau and GMD were assessed on a voxel-by-voxel basis using regression models. Age, sex, APOE ϵ4 status, diagnosis, and total intracranial volume were used as covariates where appropriate. Participants were defined as amyloid positive (Aβ) if CSF Aβ42 was <192 pg/mL. Results: Plasma tau was negatively correlated with GMD in the medial temporal lobe (MTL), precuneus, thalamus, and striatum. The associations with thalamus and striatum were independent of diagnosis. A negative correlation also existed between plasma tau and GMD in Aβ participants in the MTL, precuneus, and frontal lobe. When compared to CSF t-tau, plasma tau showed a notably different associated brain atrophy pattern, with only small overlapping regions in the fusiform gyrus. Conclusion: Plasma tau may serve as a non-specific marker for neurodegeneration but is still relevant to AD considering low GMD was associated with plasma tau in Aβ participants and not Aβ-participants.

Original languageEnglish (US)
Pages (from-to)1245-1254
Number of pages10
JournalJournal of Alzheimer's Disease
Volume58
Issue number4
DOIs
StatePublished - 2017

Fingerprint

Atrophy
Alzheimer Disease
Brain
Cerebrospinal Fluid
Temporal Lobe
Parietal Lobe
Thalamus
Amyloid
Cognitive Dysfunction
Prodromal Symptoms
Frontal Lobe
Gray Matter

Keywords

  • Alzheimer disease
  • magnetic resonance imaging
  • mild cognitive impairment
  • plasma
  • tau protein

ASJC Scopus subject areas

  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

Cite this

Plasma Tau Association with Brain Atrophy in Mild Cognitive Impairment and Alzheimer's Disease. / for the Alzheimer Disease Neuroimaging Initiative.

In: Journal of Alzheimer's Disease, Vol. 58, No. 4, 2017, p. 1245-1254.

Research output: Contribution to journalArticle

for the Alzheimer Disease Neuroimaging Initiative. / Plasma Tau Association with Brain Atrophy in Mild Cognitive Impairment and Alzheimer's Disease. In: Journal of Alzheimer's Disease. 2017 ; Vol. 58, No. 4. pp. 1245-1254.
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title = "Plasma Tau Association with Brain Atrophy in Mild Cognitive Impairment and Alzheimer's Disease",
abstract = "Background: Peripheral (plasma) and central (cerebrospinal fluid, CSF) measures of tau are higher in Alzheimer's disease (AD) relative to prodromal stages and controls. While elevated CSF tau concentrations have been shown to be associated with lower grey matter density (GMD) in AD-specific regions, this correlation has yet to be examined for plasma in a large study. Objective: Determine the neuroanatomical correlates of plasma tau using voxel-based analysis. Methods: Cross-sectional data for 508 ADNI participants were collected for clinical, plasma total-tau (t-tau), CSF amyloid (Aβ42) and tau, and MRI variables. The relationship between plasma tau and GMD and between CSF t-tau and GMD were assessed on a voxel-by-voxel basis using regression models. Age, sex, APOE ϵ4 status, diagnosis, and total intracranial volume were used as covariates where appropriate. Participants were defined as amyloid positive (Aβ) if CSF Aβ42 was <192 pg/mL. Results: Plasma tau was negatively correlated with GMD in the medial temporal lobe (MTL), precuneus, thalamus, and striatum. The associations with thalamus and striatum were independent of diagnosis. A negative correlation also existed between plasma tau and GMD in Aβ participants in the MTL, precuneus, and frontal lobe. When compared to CSF t-tau, plasma tau showed a notably different associated brain atrophy pattern, with only small overlapping regions in the fusiform gyrus. Conclusion: Plasma tau may serve as a non-specific marker for neurodegeneration but is still relevant to AD considering low GMD was associated with plasma tau in Aβ participants and not Aβ-participants.",
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author = "{for the Alzheimer Disease Neuroimaging Initiative} and Deters, {Kacie D.} and Risacher, {Shannon L.} and Sungeun Kim and Kwangsik Nho and West, {John D.} and Kaj Blennow and Henrik Zetterberg and Shaw, {Leslie M.} and Trojanowski, {John Q.} and Weiner, {Michael W.} and Andrew Saykin",
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T1 - Plasma Tau Association with Brain Atrophy in Mild Cognitive Impairment and Alzheimer's Disease

AU - for the Alzheimer Disease Neuroimaging Initiative

AU - Deters, Kacie D.

AU - Risacher, Shannon L.

AU - Kim, Sungeun

AU - Nho, Kwangsik

AU - West, John D.

AU - Blennow, Kaj

AU - Zetterberg, Henrik

AU - Shaw, Leslie M.

AU - Trojanowski, John Q.

AU - Weiner, Michael W.

AU - Saykin, Andrew

PY - 2017

Y1 - 2017

N2 - Background: Peripheral (plasma) and central (cerebrospinal fluid, CSF) measures of tau are higher in Alzheimer's disease (AD) relative to prodromal stages and controls. While elevated CSF tau concentrations have been shown to be associated with lower grey matter density (GMD) in AD-specific regions, this correlation has yet to be examined for plasma in a large study. Objective: Determine the neuroanatomical correlates of plasma tau using voxel-based analysis. Methods: Cross-sectional data for 508 ADNI participants were collected for clinical, plasma total-tau (t-tau), CSF amyloid (Aβ42) and tau, and MRI variables. The relationship between plasma tau and GMD and between CSF t-tau and GMD were assessed on a voxel-by-voxel basis using regression models. Age, sex, APOE ϵ4 status, diagnosis, and total intracranial volume were used as covariates where appropriate. Participants were defined as amyloid positive (Aβ) if CSF Aβ42 was <192 pg/mL. Results: Plasma tau was negatively correlated with GMD in the medial temporal lobe (MTL), precuneus, thalamus, and striatum. The associations with thalamus and striatum were independent of diagnosis. A negative correlation also existed between plasma tau and GMD in Aβ participants in the MTL, precuneus, and frontal lobe. When compared to CSF t-tau, plasma tau showed a notably different associated brain atrophy pattern, with only small overlapping regions in the fusiform gyrus. Conclusion: Plasma tau may serve as a non-specific marker for neurodegeneration but is still relevant to AD considering low GMD was associated with plasma tau in Aβ participants and not Aβ-participants.

AB - Background: Peripheral (plasma) and central (cerebrospinal fluid, CSF) measures of tau are higher in Alzheimer's disease (AD) relative to prodromal stages and controls. While elevated CSF tau concentrations have been shown to be associated with lower grey matter density (GMD) in AD-specific regions, this correlation has yet to be examined for plasma in a large study. Objective: Determine the neuroanatomical correlates of plasma tau using voxel-based analysis. Methods: Cross-sectional data for 508 ADNI participants were collected for clinical, plasma total-tau (t-tau), CSF amyloid (Aβ42) and tau, and MRI variables. The relationship between plasma tau and GMD and between CSF t-tau and GMD were assessed on a voxel-by-voxel basis using regression models. Age, sex, APOE ϵ4 status, diagnosis, and total intracranial volume were used as covariates where appropriate. Participants were defined as amyloid positive (Aβ) if CSF Aβ42 was <192 pg/mL. Results: Plasma tau was negatively correlated with GMD in the medial temporal lobe (MTL), precuneus, thalamus, and striatum. The associations with thalamus and striatum were independent of diagnosis. A negative correlation also existed between plasma tau and GMD in Aβ participants in the MTL, precuneus, and frontal lobe. When compared to CSF t-tau, plasma tau showed a notably different associated brain atrophy pattern, with only small overlapping regions in the fusiform gyrus. Conclusion: Plasma tau may serve as a non-specific marker for neurodegeneration but is still relevant to AD considering low GMD was associated with plasma tau in Aβ participants and not Aβ-participants.

KW - Alzheimer disease

KW - magnetic resonance imaging

KW - mild cognitive impairment

KW - plasma

KW - tau protein

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DO - 10.3233/JAD-161114

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