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Acta neurologica Belgica
Sep, 2017;117 (3): 591-602.

Alzheimer's disease CSF biomarkers: clinical indications and rational use.

Ellis Niemantsverdriet, Sara Valckx, Maria Bjerke, Sebastiaan Engelborghs
Author Information
  1. Ellis Niemantsverdriet: Reference Center for Biological Markers of Dementia (BIODEM), Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, University of Antwerp (UAntwerp), Antwerp, Belgium.
  2. Sara Valckx: Reference Center for Biological Markers of Dementia (BIODEM), Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, University of Antwerp (UAntwerp), Antwerp, Belgium.
  3. Maria Bjerke: Reference Center for Biological Markers of Dementia (BIODEM), Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, University of Antwerp (UAntwerp), Antwerp, Belgium.
  4. Sebastiaan Engelborghs: Reference Center for Biological Markers of Dementia (BIODEM), Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, University of Antwerp (UAntwerp), Antwerp, Belgium. Sebastiaan.Engelborghs@uantwerp.be. ORCID
PMID: 28752420 DOI: 10.1007/s13760-017-0816-5

Abstract

This review focusses on the validation and standardization of Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers, as well as on the current clinical indications and rational use of CSF biomarkers in daily clinical practice. The validated AD CSF biomarkers, Aβ, T-tau, and P-tau, have an added value in the (differential) diagnosis of AD and related disorders, including mixed pathologies, atypical presentations, and in case of ambiguous clinical dementia diagnosis. CSF biomarkers should not be routinely used in the diagnostic work-up of dementia and cannot be used to diagnose non-AD dementias. In cognitively healthy subjects, CSF biomarkers can only be applied for research purposes, e.g., to identify pre-clinical AD in the context of clinical trials with potentially disease-modifying drugs. Therefore, biomarker-based early diagnosis of AD offers great opportunities for preventive treatment development in the near future.

Keywords

Alzheimer’s disease Amyloid-β Biomarkers Cerebrospinal fluid Dementia Tau

References

  1. Alzheimers Dement. 2017 Mar;13(3):274-284 [PMID: 28341065]
  2. Alzheimers Dement (Amst). 2017 May 18;8:111-126 [PMID: 28603768]
  3. Alzheimers Dement. 2017 Aug;13(8):885-892 [PMID: 28222302]
  4. Nature. 2016 Aug 31;537(7618):50-6 [PMID: 27582220]
  5. Neurology. 2012 Oct 9;79(15):1591-8 [PMID: 23019264]
  6. Brain. 2016 Sep;139(Pt 9):2540-53 [PMID: 27401520]
  7. N Engl J Med. 2009 May 28;360(22):2302-9 [PMID: 19474427]
  8. Neurobiol Aging. 2008 Aug;29(8):1143-59 [PMID: 17428581]
  9. Arch Neurol. 2001 Mar;58(3):373-9 [PMID: 11255440]
  10. Brain. 2006 Nov;129(Pt 11):3035-41 [PMID: 17012293]
  11. Acta Neuropathol. 2017 Apr;133(4):559-578 [PMID: 28205010]
  12. Int J Alzheimers Dis. 2010 Jul 15;2010: [PMID: 20798852]
  13. Continuum (Minneap Minn). 2016 Apr;22(2 Dementia):404-18 [PMID: 27042901]
  14. Clin Chim Acta. 2015 Sep 20;449:9-15 [PMID: 26141614]
  15. Lancet Neurol. 2012 Aug;11(8):669-78 [PMID: 22749065]
  16. Lancet Neurol. 2006 Mar;5(3):228-34 [PMID: 16488378]
  17. Arch Gen Psychiatry. 2012 Jan;69(1):98-106 [PMID: 22213792]
  18. Alzheimers Dement. 2014 Nov;10(6):844-52 [PMID: 24798886]
  19. Lancet Neurol. 2016 Jun;15(7):673-684 [PMID: 27068280]
  20. J Intern Med. 2004 Sep;256(3):183-94 [PMID: 15324362]
  21. J Alzheimers Dis. 2013;35(1):137-46 [PMID: 23364139]
  22. J Alzheimers Dis. 2013;33(3):807-22 [PMID: 23034521]
  23. Brain. 2015 Sep;138(Pt 9):2701-15 [PMID: 26220940]
  24. J Alzheimers Dis. 2016 Jul 6;53(4):1523-38 [PMID: 27392859]
  25. Neurobiol Aging. 1998 Mar-Apr;19(2):109-16 [PMID: 9558143]
  26. Alzheimers Dement. 2015 Dec;11(12):1461-1469 [PMID: 26092348]
  27. Alzheimers Dement. 2011 May;7(3):270-9 [PMID: 21514249]
  28. Nat Rev Neurol. 2010 Mar;6(3):131-44 [PMID: 20157306]
  29. Neuron. 2013 Dec 18;80(6):1347-58 [PMID: 24360540]
  30. Lancet Neurol. 2011 Mar;10(3):230-40 [PMID: 21317042]
  31. Alzheimers Dement. 2017 Apr;13(4):e1-e85 [PMID: 28342697]
  32. Alzheimers Dement. 2017 Mar;13(3):285-295 [PMID: 28341066]
  33. Alzheimers Dement. 2014 Nov;10(6):808-17 [PMID: 25150736]
  34. J Alzheimers Dis. 2015;45(4):1039-43 [PMID: 25633672]
  35. J Am Med Dir Assoc. 2016 May 1;17(5):452-3 [PMID: 26972349]
  36. Am J Geriatr Psychiatry. 2008 Jul;16(7):603-11 [PMID: 18591580]
  37. Alzheimers Dement. 2014 Oct;10(5 Suppl):S290-8 [PMID: 24439167]
  38. J Neurol Sci. 2011 Jan 15;300(1-2):63-6 [PMID: 20965516]
  39. Alzheimers Dement. 2013 May;9(3):251-61 [PMID: 23622690]
  40. J Alzheimers Dis. 2018;63(1):373-381 [PMID: 29614653]
  41. Brain Res. 2010 Nov 29;1362:13-22 [PMID: 20875798]
  42. Ann Neurol. 2009 Aug;66(2):245-9 [PMID: 19743453]
  43. JAMA. 2009 Jul 22;302(4):385-93 [PMID: 19622817]
  44. J Nucl Med. 2017 Sep;58(9):1483-1489 [PMID: 28336779]
  45. JAMA. 2003 Apr 23-30;289(16):2094-103 [PMID: 12709467]
  46. Alzheimers Dement. 2016 Feb;12(2):154-163 [PMID: 26368321]
  47. Lancet Neurol. 2014 Jun;13(6):614-29 [PMID: 24849862]
  48. Neurology. 2011 Mar 15;76(11):1006-14 [PMID: 21325651]
  49. J Alzheimers Dis. 2013;33(1):117-31 [PMID: 22936010]
  50. JAMA Neurol. 2015 Mar;72(3):267-75 [PMID: 25559883]
  51. JAMA Neurol. 2016 May 1;73(5):561-71 [PMID: 27018940]
  52. Brain. 2015 May;138(Pt 5):1327-38 [PMID: 25693589]
  53. Biomark Med. 2016;10(1):19-34 [PMID: 26314196]
  54. Neurology. 2001 May 8;56(9):1143-53 [PMID: 11342678]
  55. Neurobiol Aging. 2010 Nov;31(11):1867-76 [PMID: 19150153]
  56. J Alzheimers Dis. 2013;36(4):759-67 [PMID: 23666174]
  57. J Alzheimers Dis. 2015;45(3):813-22 [PMID: 25633670]
  58. Alzheimers Dement. 2012 Nov;8(6):553-9 [PMID: 23102125]
  59. J Alzheimers Dis. 2016;51(1):97-106 [PMID: 26836187]
  60. Biomark Med. 2012 Aug;6(4):419-30 [PMID: 22917144]
  61. Alzheimers Dement. 2017 Sep;13(9):1013-1023 [PMID: 28263741]
  62. J Alzheimers Dis. 2011;27(3):665-76 [PMID: 21860087]
  63. Neurobiol Aging. 2015 Sep;36(9):2587-96 [PMID: 26093515]
  64. J Cent Nerv Syst Dis. 2014 May 19;6:51-8 [PMID: 24932109]
  65. J Alzheimers Dis. 2016 Aug 10;54(1):383-95 [PMID: 27567807]
  66. Alzheimers Dement. 2012 Jan;8(1):65-73 [PMID: 22047631]
  67. Brain. 2007 Sep;130(Pt 9):2320-6 [PMID: 17586559]
  68. Neurology. 1984 Jul;34(7):939-44 [PMID: 6610841]
  69. Lancet Neurol. 2012 Feb;11(2):170-8 [PMID: 22265212]
  70. J Alzheimers Dis. 2017;60(2):561-576 [PMID: 28869470]
  71. Mov Disord. 2011 Jul;26(8):1428-35 [PMID: 21469206]
  72. J Neurol. 2015 Dec;262(12):2722-30 [PMID: 26410752]
  73. Acta Neuropathol. 2009 Feb;117(2):125-36 [PMID: 19139911]
  74. Alzheimers Dement. 2011 May;7(3):263-9 [PMID: 21514250]
  75. J Neurol. 2012 Nov;259(11):2429-33 [PMID: 22576334]
  76. Arch Neurol. 2010 Aug;67(8):949-56 [PMID: 20697045]
  77. Clin Chem. 2015 May;61(5):734-43 [PMID: 25869575]
  78. Science. 2006 Oct 6;314(5796):130-3 [PMID: 17023659]
  79. Clin Chem Lab Med. 2016 Jul 1;54(7):1177-91 [PMID: 26495928]
  80. Alzheimers Dement. 2011 May;7(3):280-92 [PMID: 21514248]
  81. JAMA. 2015 May 19;313(19):1924-38 [PMID: 25988462]
  82. Front Neurol. 2015 Aug 19;6:179 [PMID: 26347708]

Grants

  1. 115372/EU/EFPIA Innovative Medicines Initiative Joint Undertaking

MeSH Term

Alzheimer Disease
Amyloid beta-Peptides
Biomarkers
Early Diagnosis
Humans
Peptide Fragments
tau Proteins

Chemicals

Amyloid beta-Peptides
Biomarkers
Peptide Fragments
amyloid beta-protein (1-42)
tau Proteins
Journal Article Review
Article has an altmetric score of 49

Word Cloud

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