An aberrant protein complex in CSF as a biomarker of Alzheimer disease

M. A. Lovell, B. C. Lynn, S. Xiong, Joseph Quinn, Jeffrey Kaye, W. R. Markesbery

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Objective:: To determine if an aberrant protein complex consisting of prostaglandin-d-synthase (PDS) and transthyretin (TTR) in CSF differentiates between subjects with Alzheimer disease (AD) and normal control (NC) subjects. Methods:: Western blot analysis and a unique sandwich ELISA were used to quantify levels of complexed PDS/TTR in ventricular CSF of subjects with autopsy-verified diagnoses and in lumbar CSF of living subjects with mild to moderate probable AD and age-matched NC subjects. Ventricular CSF was obtained from short postmortem interval autopsies of 7 NC subjects (4 men/3 women), 12 diseased control (DC) subjects (7 men/5 women), 4 subjects with mild cognitive impairment (MCI) (2 men/2 women), and 8 subjects with late-stage AD (LAD) (4 men/4 women). Lumbar CSF was obtained from 15 subjects with probable AD (5 men/10 women) and 14 age-matched NC subjects (10 men/4 women) and was analyzed in a double-blind fashion. Results:: A significant increase in complexed PDS/TTR in ventricular CSF was found in MCI and LAD subjects but not DC subjects compared with NC subjects. Double-blind analysis of complexed PDS/TTR in lumbar CSF showed a significant sixfold increase in levels of the PDS/TTR complex in living probable AD subjects compared with age-matched NC subjects and a 100% sensitivity and 93% specificity in the identification of subjects with AD. Conclusion:: After further study of larger numbers of patients, quantifying prostaglandin-d-synthase/transthyretin complex in CSF may be useful in the diagnosis of Alzheimer disease, possibly in the early stages of the disease.

Original languageEnglish (US)
Pages (from-to)2212-2218
Number of pages7
JournalNeurology
Volume70
Issue number23
DOIs
StatePublished - Jun 3 2008

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Prealbumin
Prostaglandin-Endoperoxide Synthases
Alzheimer Disease
Biomarkers
Proteins
Autopsy
Western Blotting
Enzyme-Linked Immunosorbent Assay
Sensitivity and Specificity

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

An aberrant protein complex in CSF as a biomarker of Alzheimer disease. / Lovell, M. A.; Lynn, B. C.; Xiong, S.; Quinn, Joseph; Kaye, Jeffrey; Markesbery, W. R.

In: Neurology, Vol. 70, No. 23, 03.06.2008, p. 2212-2218.

Research output: Contribution to journalArticle

Lovell, M. A. ; Lynn, B. C. ; Xiong, S. ; Quinn, Joseph ; Kaye, Jeffrey ; Markesbery, W. R. / An aberrant protein complex in CSF as a biomarker of Alzheimer disease. In: Neurology. 2008 ; Vol. 70, No. 23. pp. 2212-2218.
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abstract = "Objective:: To determine if an aberrant protein complex consisting of prostaglandin-d-synthase (PDS) and transthyretin (TTR) in CSF differentiates between subjects with Alzheimer disease (AD) and normal control (NC) subjects. Methods:: Western blot analysis and a unique sandwich ELISA were used to quantify levels of complexed PDS/TTR in ventricular CSF of subjects with autopsy-verified diagnoses and in lumbar CSF of living subjects with mild to moderate probable AD and age-matched NC subjects. Ventricular CSF was obtained from short postmortem interval autopsies of 7 NC subjects (4 men/3 women), 12 diseased control (DC) subjects (7 men/5 women), 4 subjects with mild cognitive impairment (MCI) (2 men/2 women), and 8 subjects with late-stage AD (LAD) (4 men/4 women). Lumbar CSF was obtained from 15 subjects with probable AD (5 men/10 women) and 14 age-matched NC subjects (10 men/4 women) and was analyzed in a double-blind fashion. Results:: A significant increase in complexed PDS/TTR in ventricular CSF was found in MCI and LAD subjects but not DC subjects compared with NC subjects. Double-blind analysis of complexed PDS/TTR in lumbar CSF showed a significant sixfold increase in levels of the PDS/TTR complex in living probable AD subjects compared with age-matched NC subjects and a 100{\%} sensitivity and 93{\%} specificity in the identification of subjects with AD. Conclusion:: After further study of larger numbers of patients, quantifying prostaglandin-d-synthase/transthyretin complex in CSF may be useful in the diagnosis of Alzheimer disease, possibly in the early stages of the disease.",
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AU - Markesbery, W. R.

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