Dement Neurocogn Disord.  2013 Mar;12(1):1-8. 10.12779/dnd.2013.12.1.1.

Preliminary Study for a Multicenter Study of Alzheimer's Disease Cerebrospinal Fluid Biomarkers

Affiliations
  • 1Department of Neurology, Soonchunhyang University Bucheon Hospital, Bucheon, Korea.
  • 2Department of Neurology, Ilsan Hospital, National Health Insurance Corporation, Goyang, Korea.
  • 3Department of Anesthesiology, Soonchunhyang University Bucheon Hospital, Bucheon, Korea.
  • 4Department of Orthopedic Surgery, Soonchunhyang University Bucheon Hospital, Bucheon, Korea.
  • 5Department of Neurology, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Korea.
  • 6Department of Neurology, Inha University School of Medicine, Incheon, Korea. seonghye@inha.ac.kr

Abstract

BACKGROUND
The usefulness of cerebrospinal fluid (CSF) concentrations of amyloid beta protein 1-42 (Abeta42), phosphorylated tau (pTau) and total tau (tTau) have been increasing in Alzheimer's disease (AD). However, the direct adoption of previously reported standard values is not appropriate due to interlaboratory variability. We started this study to set up an accessible system to measure CSF biomarkers in our country with high reproducibility and validity.
METHODS
Including CSFs from four different institutes the levels of Abeta42, pTau181 and tTau were measured in one lab. The intertest variability and difference in the levels of biomarkers depending on diseases were assessed. Through analysis of receiver operating characteristic cut points and binary logistic regression the cut-off values of Abeta42, pTau and tTau level were obtained, and their validity was evaluated.
RESULTS
The intertest consistency was high in measuring CSF biomarkers. The value of Abeta42 was markedly decreased in AD (n= 17) and other dementia (n= 9) compared to normal control (n= 12). The levels of pTau181 and tTau were high in AD, but not in other dementia and normal control. The threshold values of Abeta42, pTau181 and tTau were 290.3 pg/mL, 54.3 pg/mL, and 320.7 pg/mL in differentiating AD from normal control showing high sensitivity and specificity. Especially, the ratios of pTau181/Abeta42 (> 0.16) and tTau/Abeta42 (> 0.76) showed the prime validity.
CONCLUSIONS
Our data of CSF Abeta42, pTau181, and tTau levels were highly reproducible. PTau181/Abeta42 and tTau/Abeta42 ratios were the greatly helpful in differentiating AD from normal control.

Keyword

Alzheimer's disease; Amyloid beta protein; Biomarker; Enzyme-linked immunosorbent assay; Cerebrospinal fluid; Tau

MeSH Terms

Academies and Institutes
Adoption
Alzheimer Disease
Amyloid beta-Peptides
Biomarkers
Dementia
Enzyme-Linked Immunosorbent Assay
Logistic Models
Pyridines
ROC Curve
Sensitivity and Specificity
Thiazoles
Amyloid beta-Peptides
Pyridines
Thiazoles

Cited by  4 articles

A Consensus in Korea Regarding a Protocol to Reduce Preanalytical Sources of Variability in the Measurement of the Cerebrospinal Fluid Biomarkers of Alzheimer's Disease
Sun Ah Park, Ju-Hee Kang, Eun-Suk Kang, Chang-Seok Ki, Jee Hoon Roh, Young Chul Youn, Seong Yoon Kim, Sang Yun Kim
J Clin Neurol. 2015;11(2):132-141.    doi: 10.3988/jcn.2015.11.2.132.

Efficacy of the Phosphorylated tau 181 in Differential Diagnosis of the Alzheimer's Disease: A Systematic Review and Meta-Analysis
Jin-A Mo, Jae-Won Jang, Ju-Hee Lim, Min Lee, Ah-Ram Sul, Hee-Jin Kim, Young Chul Youn
Dement Neurocogn Disord. 2014;13(4):129-138.    doi: 10.12779/dnd.2014.13.4.129.

Atypical Early-Onset Alzheimer's Disease Dementia Diagnosed by Biomarker Study
Seung-Keun Lee, Dae-Seop Shin, Ho-Sik Shin, Jun-Hyun Kim, Sun Ah Park
Dement Neurocogn Disord. 2015;14(4):168-171.    doi: 10.12779/dnd.2015.14.4.168.

Atypical Early-Onset Alzheimer's Disease Dementia Diagnosed by Biomarker Study
Seung-Keun Lee, Dae-Seop Shin, Ho-Sik Shin, Jun-Hyun Kim, Sun Ah Park
Dement Neurocogn Disord. 2015;14(4):168-171.    doi: 10.12779/dnd.2015.14.4.168.


Reference

1. Aisen PS, Andrieu S, Sampaio C, Carrillo M, Khachaturian ZS, Dubois B, et al. Report of the task force on designing clinical trials in early (predementia) AD. Neurology. 2011. 76:280–286.
Article
2. Golde TE, Schneider LS, Koo EH. Anti-aβ therapeutics in Alzheimer's disease: the need for a paradigm shift. Neuron. 2011. 69:203–213.
Article
3. Cummings JL. Biomarkers in Alzheimer's disease drug development. Alzheimers Dement. 2011. 7:e13–e44.
Article
4. Mueller SG, Weiner MW, Thal LJ, Petersen RC, Jack CR, Jugust W, et al. Ways toward an early diagnosis in Alzheimer's disease: the Alzheimer's disease Neuroimaging Initiative (ADNI). Alzheimers Dement. 2005. 1:55–66.
Article
5. Choi J, Lee HW, Suk K. Plasma level of chitinase 3-like 1 protein increases in patients with early Alzheimer's disease. J Neurol. 2011. 258:2181–2185.
Article
6. Han SH, Jung ES, Sohn JH, Hong HJ, Hong HS, Kim JW, et al. Human serum transthyretin levels correlate inversely with Alzheimer's disease. J Alzheimers Dis. 2011. 25:77–84.
Article
7. Kim SM, Song J, Kim S, Han C, Park MH, Koh Y, et al. Identification of peripheral inflammatory markers between normal control and Alzheimer's disease. BMC Neurol. 2011. 11:51.
Article
8. Lee KS, Chung JH, Lee KH, Shin MJ, Oh BH, Hong CH. Bioplex analysis of plasma cytokines in Alzheimer's disease and mild cognitive impairment. Immunol Lett. 2008. 121:105–109.
Article
9. Lee JW, Namkoong H, Kim HK, Kim S, Hwang DW, Na HR, et al. Fibrinogen gamma-A chain precursor in CSF: a candidate biomarker for Alzheimer's disease. BMC Neurol. 2007. 7:14.
Article
10. Holtzman DM. CSF biomarkers for Alzheimer's disease: current utility and potential future use. Neurobiol Aging. 2011. 32:S4–S9.
Article
11. Zetterberg H, Blennow K, Hanse E. Amyloid beta and APP as biomarkers for Alzheimer's disease. Exp Gerontol. 2010. 45:23–29.
Article
12. Blennow K, Vanmechelen E, Hampel H. CSF total tau, Abeta42 and phosphorylated tau protein as biomarkers for Alzheimer's disease. Mol Neurobiol. 2001. 24:87–97.
Article
13. Buerger K, Zinkowski R, Teipel SJ, Tapiola T, Arai H, Blennow K, et al. Differential diagnosis of Alzheimer disease with cerebrospinal fluid levels of tau protein phosphorylated at threonine 231. Arch Neurol. 2002. 59:1267–1272.
Article
14. Shaw LM, Vanderstichele H, Knapik-Czajka M, Clark CM, Aisen PS, Petersen RC, et al. Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects. Ann Neurol. 2009. 65:403–413.
Article
15. Welge V, Fiege O, Lewczuk P, Mollenhauer B, Esselmann H, Klafki HW, et al. Combined CSF tau, p-tau181 and amyloid-beta 38/40/42 for diagnosing Alzheimer's disease. J Neural Transm. 2009. 116:203–212.
Article
16. Lee EH, Youn YC, Park KY, Min JH, Kwon OS, Lee HO, et al. The effect of acetylcholine esterase inhibitor on cerebrospinal fluid β-amyloid 1-42 and phosphorylated tau protein in Korean Alzheimer's disease patients: Preliminary study. J Korean Neurol Assoc. 2008. 26:224–230.
Article
17. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer's disease-report of the NINCDS-ADRDA work group under the auspices of Department of Health and Human Services Task Force on Alzheimer's disease. Neurology. 1984. 34:939–944.
Article
18. Dubois B, Feldman HH, Jacova C, DeKosky ST, Barberger-Gateau P, Cummings J, et al. Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS-ADRDA criteria. Lancet Neurol. 2007. 6:734–746.
Article
19. Emre M, Aarslan D, Brown R, Burn DJ, Kuyckaerts C, Mizuno Y, et al. Clinical diagnostic criteria for dementia associated with Parkinson's disease. Mov Disord. 2007. 22:1689–1707.
Article
20. McKeith IG, Dickson DW, Lowe J, Emre M, O'Brien JT, Feldman H, et al. Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology. 2005. 65:1863–1872.
Article
21. Neary D, Snowden JS, Gustafson L, Passant U, Stuss D, Black S, et al. Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology. 1998. 51:1546–1554.
Article
22. Litvan I, Agid Y, Calne D, Campbell G, Dubois B, Duvoisin RC, et al. Clinical research criteria for the diagnosis of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome): report of the NINDS-SPSP international workshop. Neurology. 1996. 47:1–9.
Article
23. Roman GC, Tatemichi TK, Erkinjuntti T, Cummings JL, Masdeu JC, Garcia JH, et al. Vascular dementia. Diagnostic criteria for research studies: Report of the NINDS-AIREN international workshop. Neurology. 1993. 43:250–260.
Article
24. Bjerke M, Portelius E, Minthon L, Wallin A, Anckarsäter H, Anckarsäter R, et al. Confounding factors influencing amyloid beta concentration in cerebrospinal fluid. Int J Alzheimers Dis. 2010. 2010:986310.
Article
25. Bateman RJ, Wen G, Morris JC, Holtzman DM. Fluctuations of CSF amyloid-β levels: Implications for a diagnostic and therapeutic biomarker. Neurology. 2007. 68:666–669.
Article
26. Verwey NA, van der Flier WM, Blennow K, Clark C, Sokolow S, De Deyn PP, et al. A wordwide multicenter comparison of assays for cerebrospinal fluid biomarkers in Alzheimer's disease. Ann Clin Biochem. 2009. 46:235–240.
Article
27. Schoonenboom NS, Reesink FE, Verwey NA, Kester MI, Teunissen CE, van de Ven PM, et al. Cerebrospinal fluid markers for differential dementia diagnosis in a large memory clinic cohort. Neurology. 2012. 78:47–54.
Article
28. Kemppainen NM, Aalto S, Karrasch M, Nagren K, Savisto N, Oikonen V, et al. Cognitive reserve hypothesis: Pittsburgh Compound B and fluorodeoxyglucose positron emission tomography in relation to education in mild Alzheimer's disease. Ann Neurol. 2008. 63:112–118.
Article
29. Motter R, Vigo-Pelfrey C, Kholodenko D, Barbour R, Johnson-Wood K, Galasko D, et al. Reduction of beta-amyloid peptide42 in the cerebrospinal fluid of patients with Alzheimer's disease. Ann Neurol. 1995. 38:643–648.
Article
30. Sunderland T, Linker G, Mirza N, Putnam KT, Friedman DL, Kimmel LH, et al. Decreased beta-amyloid 1-42 and increased tau levels in cerebrospinalfluid of patients with Alzheimer disease. JAMA. 2003. 289:2094–2103.
Article
31. Fagan AM, Mintun MA, Mach RH, Lee SY, Dence CS, Shah AR, et al. Inverse relation between in vivo amyloid imaging load and cerebrospinal fluid Abeta42 in humans. Ann Neurol. 2006. 59:512–519.
Article
32. Fagan AM, Mintun MA, Shah AR, Aldea P, Roe CM, Mach RH, et al. Cerebrospinal fluid tau and ptau(181) increase with cortical amyloid deposition in cognitively normal individuals: implications for future clinical trials of Alzheimer's disease. EMBO Mol Med. 2009. 1:371–380.
33. Weigand SD, Vemuri P, Wiste HJ, Senjem ML, Pankratz VS, Aisen PS, et al. Transforming cerebrospinal fluid Aβ42 measures into calculated Pittsburgh compound B units of brain Aβ amyloid. Alzheimers Dement. 2011. 7:133–141.
34. Englund H, Degerman Gunnarsson M, Brundin RM, Hedlund M, Kilander L, Lannfelt L, et al. Oligomerization partially explains the lowering of Abeta42 in Alzheimer's disease cerebrospinal fluid. Neurodegener Dis. 2009. 6:139–147.
35. Hampel H, Buerger K, Zinkowski R, Teipel SJ, Goernitz A, Andreasen N, et al. Measurement of phosphorylated tau epitopes in the differential diagnosis of Alzheimer disease: a comparative cerebrospinal fluid study. Arch Gen Psychiatry. 2004. 61:95–102.
36. Hu YY, He SS, Wang X, Duan QH, Grundke-Iqbal I, Iqbal K, et al. Levels of nonphosphorylated and phosphorylated tau in cerebrospinal fluid of Alzheimer's disease patients: an ultrasensitive bienzyme-substrate-recycle enzyme-linked immunosorbent assay. Am J Pathol. 2002. 160:1269–1278.
Article
37. Vemuri P, Wiste HJ, Weigand SD, Shaw LM, Trojanowski JQ, Weiner MW, et al. MRI and CSF biomarkers in normal, MCI, and AD subjects: predicting future clinical change. Neurology. 2009. 73:294–301.
Article
38. Vemuri P, Wiste HJ, Weigand SD, Knopman DS, Trojanowski JQ, Shaw LM, et al. Serial MRI and CSF biomarkers in normal aging, MCI, and AD. Neurology. 2010. 75:143–151.
Article
39. Montine TJ, Shi M, Quinn JF, Peskind ER, Craft S, Ginghina C, et al. CSF Aβ(42) and tau in Parkinson's disease with cognitive impairment. Mov Disord. 2010. 25:2682–2685.
Article
40. Rowe CC, Ng S, Ackermann U, Gong SJ, Pike K, Savage G, et al. Imaging beta-amyloid burden in aging and dementia. Neurology. 2007. 68:1718–1725.
Article
41. Lee JH, Kim SH, Kim GH, Seo SW, Park HK, Oh SJ, et al. Identification of pure subcortical vascular dementia using 11C-Pittsburgh compound B. Neurology. 2011. 77:18–25.
Article
42. Galasko D, Clark C, Chang L, Miller B, Green RC, Motter R, et at. Assessment of CSF levels of tau protein in mildly demented patients with Alzheimer's disease. Neurology. 1997. 48:632–635.
Article
43. Hulstaert F, Blennow K, Ivanoiu A, Schoonderwaldt HC, Riemenschneider M, DeDeyn PP, et al. Improved discrimination of AD patients using beta-amyloid(1-42) and tau levels in CSF. Neurology. 1999. 52:1555–1562.
Article
44. Andreasen N, Minthon L, Clarberg A, Davidsson P, Gottfries J, Vanmechelen E, et al. Sensitivity, specificity, and stability of CSF-tau in AD in a community-based patient sample. Neurology. 1999. 53:1488–1494.
Article
45. Riemenschneider M, Wagenpfeil S, Diehl J, Lautenschlager N, Theml T, Heldmann B, et al. Tau and Abeta42 protein in CSF of patients with frontotemporal degeneration. Neurology. 2002. 58:1622–1628.
Article
Full Text Links
  • DND
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr