Cerebrospinal Fluid Tau and β-Amyloid

How Well Do These Biomarkers Reflect Autopsy-Confirmed Dementia Diagnoses?

Christopher M. Clark, Sharon Xie, Jesse Chittams, Douglas Ewbank, Elaine Peskind, Douglas Galasko, John C. Morris, Daniel W. McKeel, Martin Farlow, Sharon L. Weitlauf, Joseph Quinn, Jeffrey Kaye, David Knopman, Hiroyuki Arai, Rachelle S. Doody, Charles DeCarli, Susan Leight, Virginia M Y Lee, John Q. Trojanowski

Research output: Contribution to journalArticle

282 Citations (Scopus)

Abstract

Background: Tau and β-amyloid (Aβ) are proposed diagnostic biomarkers for Alzheimer disease (AD). Previous studies report their relationship to clinical diagnoses of AD and other dementias. To understand their value as predictors of disease-specific patholody, levels determined during life must be correlated with definitive diagnoses in mixed dementia groups and cognitively normal subjects. Objectives: To correlate antemortem cerebrospinal fluid (CSF) tau and Aβ levels with definitive dementia diagnosis in a diverse group of patients; to calculate statistics for CSF tau and Aβ. Design: Prospective study. Setting: Ten clinics experienced in the diagnosis of neurodegenerative dementias. Patients: One hundred six patients with dementia and 4 cognitively normal subjects with a definitive diagnosis, and 69 clinically diagnosed cognitively normal subjects. Main Outcome Measures: Correlation of CSF tau and Aβ with final diagnosis. Results: Mean tau level was 612 pg/mL for the 74 patients with AD, 272 pg/mL for 10 patients with frontal dementia, 282 pg/mL for 3 patients with dementia with Lewy bodies, and 140 pg/mL for 73 cognitively normal control subjects. Tau was less than 334 pg/mL for 20 patients with AD. Aβ42 was reduced in patients with AD (61 fmol/mL) compared with patients with frontal dementia (133 fmol/mL) and control subjects (109 fmol/mL), but not compared with patients with dementia with Lewy bodies (14 fmol/mL) or prion disease (60 fmol/mL). Conclusions: Elevated CSF tau levels are associated with AD pathology and can help discriminate AD from other dementing disorders. However, some patients with AD have a level less than the mean ± 2 SDs of the cognitively normal cohort.

Original languageEnglish (US)
Pages (from-to)1696-1702
Number of pages7
JournalArchives of Neurology
Volume60
Issue number12
DOIs
StatePublished - Dec 2003
Externally publishedYes

Fingerprint

Amyloid
Cerebrospinal Fluid
Dementia
Autopsy
Biomarkers
Alzheimer Disease
Lewy Body Disease
Prion Diseases
Alzheimer's Disease
Outcome Assessment (Health Care)
Prospective Studies
Pathology

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Clark, C. M., Xie, S., Chittams, J., Ewbank, D., Peskind, E., Galasko, D., ... Trojanowski, J. Q. (2003). Cerebrospinal Fluid Tau and β-Amyloid: How Well Do These Biomarkers Reflect Autopsy-Confirmed Dementia Diagnoses? Archives of Neurology, 60(12), 1696-1702. https://doi.org/10.1001/archneur.60.12.1696

Cerebrospinal Fluid Tau and β-Amyloid : How Well Do These Biomarkers Reflect Autopsy-Confirmed Dementia Diagnoses? / Clark, Christopher M.; Xie, Sharon; Chittams, Jesse; Ewbank, Douglas; Peskind, Elaine; Galasko, Douglas; Morris, John C.; McKeel, Daniel W.; Farlow, Martin; Weitlauf, Sharon L.; Quinn, Joseph; Kaye, Jeffrey; Knopman, David; Arai, Hiroyuki; Doody, Rachelle S.; DeCarli, Charles; Leight, Susan; Lee, Virginia M Y; Trojanowski, John Q.

In: Archives of Neurology, Vol. 60, No. 12, 12.2003, p. 1696-1702.

Research output: Contribution to journalArticle

Clark, CM, Xie, S, Chittams, J, Ewbank, D, Peskind, E, Galasko, D, Morris, JC, McKeel, DW, Farlow, M, Weitlauf, SL, Quinn, J, Kaye, J, Knopman, D, Arai, H, Doody, RS, DeCarli, C, Leight, S, Lee, VMY & Trojanowski, JQ 2003, 'Cerebrospinal Fluid Tau and β-Amyloid: How Well Do These Biomarkers Reflect Autopsy-Confirmed Dementia Diagnoses?', Archives of Neurology, vol. 60, no. 12, pp. 1696-1702. https://doi.org/10.1001/archneur.60.12.1696
Clark, Christopher M. ; Xie, Sharon ; Chittams, Jesse ; Ewbank, Douglas ; Peskind, Elaine ; Galasko, Douglas ; Morris, John C. ; McKeel, Daniel W. ; Farlow, Martin ; Weitlauf, Sharon L. ; Quinn, Joseph ; Kaye, Jeffrey ; Knopman, David ; Arai, Hiroyuki ; Doody, Rachelle S. ; DeCarli, Charles ; Leight, Susan ; Lee, Virginia M Y ; Trojanowski, John Q. / Cerebrospinal Fluid Tau and β-Amyloid : How Well Do These Biomarkers Reflect Autopsy-Confirmed Dementia Diagnoses?. In: Archives of Neurology. 2003 ; Vol. 60, No. 12. pp. 1696-1702.
@article{7da42e57bfdd46caab73a760e7bb1df5,
title = "Cerebrospinal Fluid Tau and β-Amyloid: How Well Do These Biomarkers Reflect Autopsy-Confirmed Dementia Diagnoses?",
abstract = "Background: Tau and β-amyloid (Aβ) are proposed diagnostic biomarkers for Alzheimer disease (AD). Previous studies report their relationship to clinical diagnoses of AD and other dementias. To understand their value as predictors of disease-specific patholody, levels determined during life must be correlated with definitive diagnoses in mixed dementia groups and cognitively normal subjects. Objectives: To correlate antemortem cerebrospinal fluid (CSF) tau and Aβ levels with definitive dementia diagnosis in a diverse group of patients; to calculate statistics for CSF tau and Aβ. Design: Prospective study. Setting: Ten clinics experienced in the diagnosis of neurodegenerative dementias. Patients: One hundred six patients with dementia and 4 cognitively normal subjects with a definitive diagnosis, and 69 clinically diagnosed cognitively normal subjects. Main Outcome Measures: Correlation of CSF tau and Aβ with final diagnosis. Results: Mean tau level was 612 pg/mL for the 74 patients with AD, 272 pg/mL for 10 patients with frontal dementia, 282 pg/mL for 3 patients with dementia with Lewy bodies, and 140 pg/mL for 73 cognitively normal control subjects. Tau was less than 334 pg/mL for 20 patients with AD. Aβ42 was reduced in patients with AD (61 fmol/mL) compared with patients with frontal dementia (133 fmol/mL) and control subjects (109 fmol/mL), but not compared with patients with dementia with Lewy bodies (14 fmol/mL) or prion disease (60 fmol/mL). Conclusions: Elevated CSF tau levels are associated with AD pathology and can help discriminate AD from other dementing disorders. However, some patients with AD have a level less than the mean ± 2 SDs of the cognitively normal cohort.",
author = "Clark, {Christopher M.} and Sharon Xie and Jesse Chittams and Douglas Ewbank and Elaine Peskind and Douglas Galasko and Morris, {John C.} and McKeel, {Daniel W.} and Martin Farlow and Weitlauf, {Sharon L.} and Joseph Quinn and Jeffrey Kaye and David Knopman and Hiroyuki Arai and Doody, {Rachelle S.} and Charles DeCarli and Susan Leight and Lee, {Virginia M Y} and Trojanowski, {John Q.}",
year = "2003",
month = "12",
doi = "10.1001/archneur.60.12.1696",
language = "English (US)",
volume = "60",
pages = "1696--1702",
journal = "Archives of Neurology",
issn = "0003-9942",
publisher = "American Medical Association",
number = "12",

}

TY - JOUR

T1 - Cerebrospinal Fluid Tau and β-Amyloid

T2 - How Well Do These Biomarkers Reflect Autopsy-Confirmed Dementia Diagnoses?

AU - Clark, Christopher M.

AU - Xie, Sharon

AU - Chittams, Jesse

AU - Ewbank, Douglas

AU - Peskind, Elaine

AU - Galasko, Douglas

AU - Morris, John C.

AU - McKeel, Daniel W.

AU - Farlow, Martin

AU - Weitlauf, Sharon L.

AU - Quinn, Joseph

AU - Kaye, Jeffrey

AU - Knopman, David

AU - Arai, Hiroyuki

AU - Doody, Rachelle S.

AU - DeCarli, Charles

AU - Leight, Susan

AU - Lee, Virginia M Y

AU - Trojanowski, John Q.

PY - 2003/12

Y1 - 2003/12

N2 - Background: Tau and β-amyloid (Aβ) are proposed diagnostic biomarkers for Alzheimer disease (AD). Previous studies report their relationship to clinical diagnoses of AD and other dementias. To understand their value as predictors of disease-specific patholody, levels determined during life must be correlated with definitive diagnoses in mixed dementia groups and cognitively normal subjects. Objectives: To correlate antemortem cerebrospinal fluid (CSF) tau and Aβ levels with definitive dementia diagnosis in a diverse group of patients; to calculate statistics for CSF tau and Aβ. Design: Prospective study. Setting: Ten clinics experienced in the diagnosis of neurodegenerative dementias. Patients: One hundred six patients with dementia and 4 cognitively normal subjects with a definitive diagnosis, and 69 clinically diagnosed cognitively normal subjects. Main Outcome Measures: Correlation of CSF tau and Aβ with final diagnosis. Results: Mean tau level was 612 pg/mL for the 74 patients with AD, 272 pg/mL for 10 patients with frontal dementia, 282 pg/mL for 3 patients with dementia with Lewy bodies, and 140 pg/mL for 73 cognitively normal control subjects. Tau was less than 334 pg/mL for 20 patients with AD. Aβ42 was reduced in patients with AD (61 fmol/mL) compared with patients with frontal dementia (133 fmol/mL) and control subjects (109 fmol/mL), but not compared with patients with dementia with Lewy bodies (14 fmol/mL) or prion disease (60 fmol/mL). Conclusions: Elevated CSF tau levels are associated with AD pathology and can help discriminate AD from other dementing disorders. However, some patients with AD have a level less than the mean ± 2 SDs of the cognitively normal cohort.

AB - Background: Tau and β-amyloid (Aβ) are proposed diagnostic biomarkers for Alzheimer disease (AD). Previous studies report their relationship to clinical diagnoses of AD and other dementias. To understand their value as predictors of disease-specific patholody, levels determined during life must be correlated with definitive diagnoses in mixed dementia groups and cognitively normal subjects. Objectives: To correlate antemortem cerebrospinal fluid (CSF) tau and Aβ levels with definitive dementia diagnosis in a diverse group of patients; to calculate statistics for CSF tau and Aβ. Design: Prospective study. Setting: Ten clinics experienced in the diagnosis of neurodegenerative dementias. Patients: One hundred six patients with dementia and 4 cognitively normal subjects with a definitive diagnosis, and 69 clinically diagnosed cognitively normal subjects. Main Outcome Measures: Correlation of CSF tau and Aβ with final diagnosis. Results: Mean tau level was 612 pg/mL for the 74 patients with AD, 272 pg/mL for 10 patients with frontal dementia, 282 pg/mL for 3 patients with dementia with Lewy bodies, and 140 pg/mL for 73 cognitively normal control subjects. Tau was less than 334 pg/mL for 20 patients with AD. Aβ42 was reduced in patients with AD (61 fmol/mL) compared with patients with frontal dementia (133 fmol/mL) and control subjects (109 fmol/mL), but not compared with patients with dementia with Lewy bodies (14 fmol/mL) or prion disease (60 fmol/mL). Conclusions: Elevated CSF tau levels are associated with AD pathology and can help discriminate AD from other dementing disorders. However, some patients with AD have a level less than the mean ± 2 SDs of the cognitively normal cohort.

UR - http://www.scopus.com/inward/record.url?scp=0346124139&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0346124139&partnerID=8YFLogxK

U2 - 10.1001/archneur.60.12.1696

DO - 10.1001/archneur.60.12.1696

M3 - Article

VL - 60

SP - 1696

EP - 1702

JO - Archives of Neurology

JF - Archives of Neurology

SN - 0003-9942

IS - 12

ER -