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. 2007 Jan 23;21(1):24–33. doi: 10.1002/jcla.20159

Competitive ELISA studies of neural thread protein in urine in Alzheimer's disease

Susanna Levy 1,✉, Matthew McConville 2, Glorie A Lazaro 2, Paul Averback 2
PMCID: PMC6649306  PMID: 17245761

Abstract

A specific and reliable competitive affinity assay kit has been developed to quantitatively measure neural thread protein (NTP) in first morning urine samples. This assay, called the urine neural thread protein test (UNTP), is a competitive enzyme‐linked immunosorbent assay (ELISA) format affinity assay using 32‐well microtiter plates. The assay detects UNTP in the 10–60 µg/mL range (an improvement over earlier assays of 103 × ), is linear and more reproducible (average coefficient of variation [CV] 6.2% in precision studies).The utility of the assay has been demonstrated in urine samples from patients with Alzheimer's disease (AD) and controls (sensitivity of 90% and specificity of 91%). Test–retest assays of subjects with AD and controls were comparatively stable at intervals of 2 days to 4.5 years, which suggests that positive (elevated) or negative (normal) NTP levels do not fluctuate significantly over time with respect to the cutoff. J. Clin. Lab. Anal. 21:24–33, 2007. © 2007 Wiley‐Liss, Inc.

Keywords: brain, neuron, neurodegeneration, protein, dementia, diagnosis

REFERENCES

  • 1. Hebert LE, Scherr PA, Bienias JL, Bennett DA, Evans DA. Alzheimer disease in the US population: prevalence estimates using the 2000 Census. Arch Neurol 2003;60:1119–1122. [DOI] [PubMed] [Google Scholar]
  • 2. Cummings JL. Alzheimer's disease. N Engl J Med 2004;351:56–67. [DOI] [PubMed] [Google Scholar]
  • 3. Jorst BC, Grossberg GT. The natural history of Alzheimer's disease: a brain bank study. J Am Geriatr Soc 1995;43:1248–1255. [DOI] [PubMed] [Google Scholar]
  • 4. Myers RH, Schaefer EJ, Wilson PWF, et al. Apolipoprotein EE4 association with dementia in a population‐based study: the Framingham study. Neurology 1996;46:673–677. [DOI] [PubMed] [Google Scholar]
  • 5. Pirtilla T, Kim KS, Mehta PD, et al. Soluble amyloid‐β‐protein in the cerebrospinal fluid of patients with Alzheimer's disease, vascular dementia and controls. J Neurol Sci 1994;127:90–95. [DOI] [PubMed] [Google Scholar]
  • 6. Jensen M, Basun H, Lannfelt L. Increased cerebrospinal fluid tau in patients with Alzheimer's disease. Neurosci Lett 1995;186:189–191. [DOI] [PubMed] [Google Scholar]
  • 7. Arai H, Terajima M, Miura M, et al. Tau in cerebrospinal fluid: a potential diagnostic marker in Alzheimer's disease. Ann Neurol 1995;38:649–652. [DOI] [PubMed] [Google Scholar]
  • 8. Motter R, Vigo‐Pelfrey C, Kholodenko D, et al. Reduction of β‐amyloid peptide 42 in the cerebrospinal fluid of patients with Alzheimer's disease. Ann Neurol 1995;38:643–648. [DOI] [PubMed] [Google Scholar]
  • 9. Munroe WA, Southwick PC, Chang L, et al. Tau protein in cerebrospinal fluid as an aid in the diagnosis of Alzheimer's disease. Ann Clin Sci 1995;25:207–217. [PubMed] [Google Scholar]
  • 10. Nitsch RM, Rebeck W, Deng M, et al. Cerebrospinal fluid levels of amyloid β‐protein in Alzheimer's disease: inverse correlation with severity of dementia and effect of apolipoprotein E genotypes. Ann Neurol 1995;37:512–518. [DOI] [PubMed] [Google Scholar]
  • 11. Tata RE, Frank A, Hemanz A. Tau protein concentrations in cerebrospinal fluid of patients with dementia of the Alzheimer type. J Neurol Neurosurg Psychiatry 1995;45:778–793. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12. van Gool WA, Kuiper MA, Wolstra GJM, et al. Concentration of amyloid β‐protein in cerebrospinal fluid of patients with Alzheimer's disease. Ann Neurol 1995;37:277–279. [DOI] [PubMed] [Google Scholar]
  • 13. Iwatsubo T. Amyloid β‐protein in plasma as a diagnostic marker for Alzheimer's disease. Neurobiol Aging 1998;19:161–163. [DOI] [PubMed] [Google Scholar]
  • 14. Pirtilla T, Mehta PD, Soininen H, et al. Cerebrospinal fluid concentrations of soluble amyloid β‐protein and apolipoprotein E in patients with Alzheimer's disease. Arch Neurol 1996;53:189–193. [DOI] [PubMed] [Google Scholar]
  • 15. Lovell MA, Markesbery WR. Ratio of 8‐hydroxyguanine in intact DNA to free 8‐hydroxyguanine is increased in Alzheimer disease ventricular cerebrospinal fluid. Arch Neurol 2001;58:392–396. [DOI] [PubMed] [Google Scholar]
  • 16. Schipper HM, Chertkow H, Mehindate K, et al. Evaluation of hemeoxygenase‐1 as a systemic biological marker of sporadic AD. Neurology 2000;54:1297–1304. [DOI] [PubMed] [Google Scholar]
  • 17. Diaz R. New biochemical markers in Alzheimer disease. Arch Neurol 2001;58:354–356. [DOI] [PubMed] [Google Scholar]
  • 18. Molsa PK, Paljarvi L, Rinne JO, et al. Validity of clinical diagnosis in dementia: a prospective clinicopathological study. J Neurol Neurosurg Psychiatry 1985;48:1085–1090. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19. Rocca WA, Amaducci LA, Schoenberg BS. Epidemiology of clinically diagnosed Alzheimer's disease. Ann Neurol 1986;19:415–424. [DOI] [PubMed] [Google Scholar]
  • 20. Burns A, Luthert P, Levy R, et al. Accuracy of clinical diagnosis of Alzheimer's disease. BMJ 1990;301:1026. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21. Corey‐Bloom J, Thal LJ, Galasko D, et al. Diagnosis and evaluation of dementia. Neurology 1995;45:211–218. [DOI] [PubMed] [Google Scholar]
  • 22. Lannfelt L. Biochemical diagnostic markers to detect early Alzheimer's disease. Neurobiol Aging 1998;19:165–167. [DOI] [PubMed] [Google Scholar]
  • 23. Sandson TA, Price BH. Diagnostic testing in neurology In: Evans RW, editor. Alzheimer's disease. Philadelphia: WB Saunders; 1999. p 31–39. [Google Scholar]
  • 24. de la Monte SM, Ghanbari K, Frey WH, et al. Characterization of the AD7C‐NTP cDNA expression in Alzheimer's disease and measurement of a 41‐kD protein in cerebrospinal fluid. J Clin Invest 1997;100:3093–3104. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25. de la Monte SM, Xu YY, Wands JR. Modulation of neuronal thread protein expression with neuritic sprouting: relevance to Alzheimer's disease. J Neurol Sci 1996;138:26–35. [DOI] [PubMed] [Google Scholar]
  • 26. de la Monte SM, Carlson RI, Brown NV, Wands JR. Profiles of neuronal thread protein expression in Alzheimer's disease. J Neuropathol Exp Neurol 1996;55:1038–1050. [PubMed] [Google Scholar]
  • 27. de la Monte SM, Wands JR. Alzheimer‐associated neuronal thread protein‐induced apoptosis and impaired mitochondrial function in human central nervous system‐derived neuronal cells. J Neuropathol Exp Neurol 2001;60:195–207. [DOI] [PubMed] [Google Scholar]
  • 28. Kahle PJ, Jakowec M, Teipel SJ, et al. Combined assessment of Tau and neuronal thread protein in Alzheimer's disease CSF. Neurology 2000;54:1498–1504. [DOI] [PubMed] [Google Scholar]
  • 29. Munzar M, Levy S, Rush R, et al. Competitive ELISA format urinary assay of neural thread protein in Alzheimer's disease. Alzheimers Rep 2001;4:61–65. [Google Scholar]
  • 30. Munzar M, McConville M, Yung J, et al. A retrospective clinical study of urinary neural thread protein in Alzheimer's disease. Alzheimers Rep 2002:5:1–6. [Google Scholar]
  • 31. Callahan CM, Hendrie HC, Tierney WM. Documentation and evaluation of cognitive impairment in elderly primary care patients. Ann Int Med 1995;122:422–429. [DOI] [PubMed] [Google Scholar]
  • 32. Valcour VG, Masaki KH, Curb JD, Blanchette PL. The detection of dementia in the primary care setting. Arch Int Med 2000;160:2964–2968. [DOI] [PubMed] [Google Scholar]
  • 33. O'Connor DW, Pallitt PA, Hyde JB et al. Do general practicioners miss dementia in elderly patients? BMJ 1988;297:1107–1110. [DOI] [PMC free article] [PubMed] [Google Scholar]

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