Skip to main content

Advertisement

Log in

Cerebrospinal fluid biomarkers of Alzheimer’s disease

  • Review
  • Published:
Neuroscience Bulletin Aims and scope Submit manuscript

Abstract

Alzheimer’s disease (AD) is a fatal neurodegenerative disorder that takes about a decade to develop, making early diagnosis possible. Clinically, the diagnosis of AD is complicated, costly, and inaccurate, so it is urgent to find specific biomarkers. Due to its multifactorial nature, a panel of biomarkers for the multiple pathologies of AD, such as cerebral amyloidogenesis, neuronal dysfunction, synapse loss, oxidative stress, and inflammation, are most promising for accurate diagnosis. Highly sensitive and high-throughput proteomic techniques can be applied to develop a panel of novel biomarkers for AD. In this review, we discuss the metabolism and diagnostic performance of the well-established core candidate cerebrospinal fluid (CSF) biomarkers (β-amyloid, total tau, and hyperphosphorylated tau). Meanwhile, novel promising CSF biomarkers, especially those identified by proteomics, updated in the last five years are also extensively discussed. Furthermore, we provide perspectives on how biomarker discovery for AD is evolving.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Apostolova LG, Hwang KS, Andrawis JP, Green AE, Babakchanian S, Morra JH, et al. 3D PIB and CSF biomarker associations with hippocampal atrophy in ADNI subjects. Neurobiol Aging 2010, 31: 1284–1303.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  2. Wimo A, Prince M. World Alzheimer Report 2010: The Global Economic Impact of Dementia. London: Alzheimer’s Disease International, 2010.

    Google Scholar 

  3. Kirk A, Kertesz A. On drawing impairment in Alzheimer’s disease. Arch Neurol 1991, 48: 73–77.

    Article  PubMed  CAS  Google Scholar 

  4. Pillon B, Deweer B, Agid Y, Dubois B. Explicit memory in Alzheimer’s, Huntington’s, and Parkinson’s diseases. Arch Neurol 1993, 50: 374–379.

    Article  PubMed  CAS  Google Scholar 

  5. Price BH, Gurvit H, Weintraub S, Geula C, Leimkuhler E, Mesulam M. Neuropsychological patterns and language deficits in 20 consecutive cases of autopsy-confirmedAlzheimer’s disease. Arch Neurol 1993, 50: 931–937.

    Article  PubMed  CAS  Google Scholar 

  6. Galton CJ, Patterson K, Xuereb JH, Hodges JR. Atypical and typical presentations of Alzheimer’s disease: a clinical, neuropsychological, neuroimaging and pathological study of 13 cases. Brain 2000, 123: 484–498.

    Article  PubMed  Google Scholar 

  7. Esteban-Santillan C, Praditsuwan R, Ueda H, Geldmacher DS. Clock drawing test in very mild Alzheimer’s disease. J Am Geriatr Soc 1998, 46: 1266–1269.

    PubMed  CAS  Google Scholar 

  8. Greene JD, Baddeley AD, Hodges JR. Analysis of the episodic memory deficit in early Alzheimer’s disease: evidence from the doors and people test. Neuropsychologia 1996, 34: 537–551.

    Article  PubMed  CAS  Google Scholar 

  9. Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science 2002, 297: 353–356.

    Article  PubMed  CAS  Google Scholar 

  10. Braak H, Braak E. Development of Alzheimer-related neurofibrillary changes in the neocortex inversely recapitulates cortical myelogenesis. Acta Neuropathol 1996, 92: 197–201.

    Article  PubMed  CAS  Google Scholar 

  11. Grundke-Iqbal I, Iqbal K, Tung YC, Quinlan M, Wisniewski HM, Binder LI. Abnormal phosphorylation of the microtubuleassociated protein tau (tau) in Alzheimer cytoskeletal pathology. Proc Natl Acad Sci U S A 1986, 83: 4913–4917.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  12. Pallas M, Camins A. Molecular and biochemical features in Alzheimer’s disease. Curr Pharm Des 2006, 12: 4389–4408.

    Article  PubMed  CAS  Google Scholar 

  13. Pappas BA, Bayley PJ, Bui BK, Hansen LA, Thal LJ. Choline acetyltransferase activity and cognitive domain scores of Alzheimer’s patients. Neurobiol Aging 2000, 21: 11–17.

    Article  PubMed  CAS  Google Scholar 

  14. Palmer AM, Stratmann GC, Procter AW, Bowen DM. Possible neurotransmitter basis of behavioral changes in Alzheimer’s disease. Ann Neurol 1988, 23: 616–620.

    Article  PubMed  CAS  Google Scholar 

  15. Bobinski M, Wegiel J, Tarnawski M, Bobinski M, Reisberg B, de Leon MJ, et al. Relationships between regional neuronal loss and neurofibrillary changes in the hippocampal formation and duration and severity of Alzheimer disease. J Neuropathol Exp Neurol 1997, 56: 414–420.

    Article  PubMed  CAS  Google Scholar 

  16. Ray S, Reddy PJ, Jain R, Gollapalli K, Moiyadi A, Srivastava S. Proteomic technologies for the identification of disease biomarkers in serum: Advances and challenges ahead. Proteomics 2011, 11: 2139–2161.

    Article  PubMed  CAS  Google Scholar 

  17. Price JL, Morris JC. Tangles and plaques in nondemented aging and “preclinical” Alzheimer’s disease. Ann Neurol 1999, 45: 358–368

    Article  PubMed  CAS  Google Scholar 

  18. Perrin RJ, Fagan AM, Holtzman DM. Multimodal techniques for diagnosis and prognosis of Alzheimer’s disease. Nature 2009, 461: 916–922.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  19. Cummings JL. Biomarkers in Alzheimer’s disease drug development. Alzheimers Dement 2011, 7: e13–44.

    Article  PubMed  CAS  Google Scholar 

  20. Blennow K. CSF biomarkers for Alzheimer’s disease: use in early diagnosis and evaluation of drug treatment. Expert Rev Mol Diagn 2005, 5: 661–672.

    Article  PubMed  CAS  Google Scholar 

  21. Evin G, Weidemann A. Biogenesis and metabolism of Alzheimer’s disease Abeta amyloid peptides. Peptides 2002, 23: 1285–1297.

    Article  PubMed  CAS  Google Scholar 

  22. Sisodia SS. Beta-amyloid precursor protein cleavage by a membrane-bound protease. Proc Natl Acad Sci U S A 1992, 89: 6075–6079.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  23. Jonsson T, Atwal JK, Steinberg S, Snaedal J, Jonsson PV, Bjornsson S, et al. A mutation in APP protects against Alzheimer/’s disease and age-related cognitive decline. Nature 2012, 488(7409): 96–99

    Article  PubMed  CAS  Google Scholar 

  24. Kang J, Lemaire HG, Unterbeck A, Salbaum JM, Masters CL, Grzeschik KH, et al. The precursor of Alzheimer’s disease amyloid A4 protein resembles a cell-surface receptor. Nature 1987, 325: 733–736.

    Article  PubMed  CAS  Google Scholar 

  25. Masters CL, Cappai R, Barnham KJ, Villemagne VL. Molecular mechanisms for Alzheimer’s disease: implications for neuroimaging and therapeutics. J Neurochem 2006, 97: 1700–1725.

    Article  PubMed  CAS  Google Scholar 

  26. McLean CA, Cherny RA, Fraser FW, Fuller SJ, Smith MJ, Beyreuther K, et al. Soluble pool of Abeta amyloid as a determinant of severity of neurodegeneration in Alzheimer’s disease. Ann Neurol 1999, 46: 860–866.

    Article  PubMed  CAS  Google Scholar 

  27. Iwatsubo T, Odaka A, Suzuki N, Mizusawa H, Nukina N, Ihara Y. Visualization of A beta 42(43) and A beta 40 in senile plaques with end-specific A beta monoclonals: evidence that an initially deposited species is A beta 42(43). Neuron 1994, 13: 45–53.

    Article  PubMed  CAS  Google Scholar 

  28. Brouillette J, Caillierez R, Zommer N, Alves-Pires C, Benilova I, Blum D, et al. Neurotoxicity and memory deficits induced by soluble low-molecular-weight amyloid-beta1–42 oligomers are revealed in vivo by using a novel animal model. J Neurosci 2012, 32: 7852–7861.

    Article  PubMed  CAS  Google Scholar 

  29. Watts JC, Giles K, Grillo SK, Lemus A, DeArmond SJ, Prusiner SB. Bioluminescence imaging of Abeta deposition in bigenic mouse models of Alzheimer’s disease. Proc Natl Acad Sci U S A 2011, 108: 2528–2533.

    Article  PubMed Central  PubMed  Google Scholar 

  30. Roher AE, Lowenson JD, Clarke S, Woods AS, Cotter RJ, Gowing E, et al. beta-Amyloid-(1–42) is a major component of cerebrovascular amyloid deposits: implications for the pathology of Alzheimer disease. Proc Natl Acad Sci U S A 1993, 90: 10836–10840.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  31. Lannfelt L, Basun H, Vigo-Pelfrey C, Wahlund LO, Winblad B, Lieberburg I, et al. Amyloid beta-peptide in cerebrospinal fluid in individuals with the Swedish Alzheimer amyloid precursor protein mutation. Neurosci Lett 1995, 199: 203–206.

    Article  PubMed  CAS  Google Scholar 

  32. Southwick PC, Yamagata SK, Echols CL, Jr., Higson GJ, Neynaber SA, Parson RE, et al. Assessment of amyloid beta protein in cerebrospinal fluid as an aid in the diagnosis of Alzheimer’s disease. J Neurochem 1996, 66: 259–265.

    Article  PubMed  CAS  Google Scholar 

  33. van Gool WA, Kuiper MA, Walstra GJ, Wolters EC, Bolhuis PA. Concentrations of amyloid beta protein in cerebrospinal fluid of patients with Alzheimer’s disease. Ann Neurol 1995, 37: 277–279.

    Article  PubMed  Google Scholar 

  34. Andreasen N, Hesse C, Davidsson P, Minthon L, Wallin A, Winblad B, et al. Cerebrospinal fluid beta-amyloid(1–42) in Alzheimer disease: differences between early- and late-onset Alzheimer disease and stability during the course of disease. Arch Neurol 1999, 56: 673–680.

    Article  PubMed  CAS  Google Scholar 

  35. Blennow K, Hampel H. CSF markers for incipient Alzheimer’s disease. Lancet Neurol 2003, 2: 605–613.

    Article  PubMed  CAS  Google Scholar 

  36. Holmes C, Boche D, Wilkinson D, Yadegarfar G, Hopkins V, Bayer A, et al. Long-term effects of Abeta42 immunisation in Alzheimer’s disease: follow-up of a randomised, placebocontrolled phase I trial. Lancet 2008, 372: 216–223.

    Article  PubMed  CAS  Google Scholar 

  37. Clark CM, Xie S, Chittams J, Ewbank D, Peskind E, Galasko D, et al. Cerebrospinal fluid tau and beta-amyloid: how well do these biomarkers reflect autopsy-confirmed dementia diagnoses? Arch Neurol 2003, 60: 1696–1702.

    Article  PubMed  Google Scholar 

  38. Engelborghs S, De Vreese K, Van de Casteele T, Vanderstichele H, Van Everbroeck B, Cras P, et al. Diagnostic performance of a CSF-biomarker panel in autopsy-confirmed dementia. Neurobiol Aging 2008, 29: 1143–1159.

    Article  PubMed  Google Scholar 

  39. Fagan AM, Roe CM, Xiong C, Mintun MA, Morris JC, Holtzman DM. Cerebrospinal fluid tau/beta-amyloid(42) ratio as a prediction of cognitive decline in nondemented older adults. Arch Neurol 2007, 64: 343–349.

    Article  PubMed  Google Scholar 

  40. Galasko D, Chang L, Motter R, Clark CM, Kaye J, Knopman D, et al. High cerebrospinal fluid tau and low amyloid beta42 levels in the clinical diagnosis of Alzheimer disease and relation to apolipoprotein E genotype. Arch Neurol 1998, 55: 937–945.

    Article  PubMed  CAS  Google Scholar 

  41. Hulstaert F, Blennow K, Ivanoiu A, Schoonderwaldt HC, Riemenschneider M, De Deyn PP, et al. Improved discrimination of AD patients using beta-amyloid(1–42) and tau levels in CSF. Neurology 1999, 52: 1555–1562.

    Article  PubMed  CAS  Google Scholar 

  42. Ida N, Hartmann T, Pantel J, Schroder J, Zerfass R, Forstl H, et al. Analysis of heterogeneous A4 peptides in human cerebrospinal fluid and blood by a newly developed sensitive Western blot assay. J Biol Chem 1996, 271: 22908–22914.

    Article  PubMed  CAS  Google Scholar 

  43. Kanai M, Matsubara E, Isoe K, Urakami K, Nakashima K, Arai H, et al. Longitudinal study of cerebrospinal fluid levels of tau, A beta1–40, and A beta1–42(43) in Alzheimer’s disease: a study in Japan. Ann Neurol 1998, 44: 17–26.

    Article  PubMed  CAS  Google Scholar 

  44. Kapaki E, Kilidireas K, Paraskevas GP, Michalopoulou M, Patsouris E. Highly increased CSF tau protein and decreased beta-amyloid (1–42) in sporadic CJD: a discrimination from Alzheimer’s disease? J Neurol Neurosurg Psychiatry 2001, 71: 401–403.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  45. Lewczuk P, Esselmann H, Otto M, Maler JM, Henkel AW, Henkel MK, et al. Neurochemical diagnosis of Alzheimer’s dementia by CSF Abeta42, Abeta42/Abeta40 ratio and total tau. Neurobiol Aging 2004, 25: 273–281.

    Article  PubMed  CAS  Google Scholar 

  46. Mehta PD, Pirttila T, Mehta SP, Sersen EA, Aisen PS, Wisniewski HM. Plasma and cerebrospinal fluid levels of amyloid beta proteins 1–40 and 1–42 in Alzheimer disease. Arch Neurol 2000, 57: 100–105.

    Article  PubMed  CAS  Google Scholar 

  47. Skoog I, Davidsson P, Aevarsson O, Vanderstichele H, Vanmechelen E, Blennow K. Cerebrospinal fluid betaamyloid 42 is reduced before the onset of sporadic dementia: a population-based study in 85-year-olds. Dement Geriatr Cogn Disord 2003, 15: 169–176

    Article  PubMed  CAS  Google Scholar 

  48. Sjogren M, Minthon L, Davidsson P, Granerus AK, Clarberg A, Vanderstichele H, et al. CSF levels of tau, beta-amyloid(1–42) and GAP-43 in frontotemporal dementia, other types of dementia and normal aging. J Neural Transm 2000, 107: 563–579.

    Article  PubMed  CAS  Google Scholar 

  49. Sjogren M, Davidsson P, Wallin A, Granerus AK, Grundstrom E, Askmark H, et al. Decreased CSF-beta-amyloid 42 in Alzheimer’s disease and amyotrophic lateral sclerosis may reflect mismetabolism of beta-amyloid induced by disparate mechanisms. Dement Geriatr Cogn Disord 2002, 13: 112–118.

    Article  PubMed  Google Scholar 

  50. Rosler N, Wichart I, Jellinger KA. Clinical significance of neurobiochemical profiles in the lumbar cerebrospinal fluid of Alzheimer’s disease patients. J Neural Transm 2001, 108: 231–246.

    Article  PubMed  CAS  Google Scholar 

  51. Andreasen N, Blennow K. beta-amyloid (A beta) protein in cerebrospinal fluid as a biomarker for Alzheimer’s disease. Peptides 2002, 23: 1205–1214.

    Article  PubMed  CAS  Google Scholar 

  52. Jensen M, Schroder J, Blomberg M, Engvall B, Pantel J, Ida N, et al. Cerebrospinal fluid A beta42 is increased early in sporadic Alzheimer’s disease and declines with disease progression. Ann Neurol 1999, 45: 504–511.

    Article  PubMed  CAS  Google Scholar 

  53. Csernansky JG, Miller JP, McKeel D, Morris JC. Relationships among cerebrospinal fluid biomarkers in dementia of the Alzheimer type. Alzheimer Dis Assoc Disord 2002, 16: 144–149.

    Article  PubMed  CAS  Google Scholar 

  54. Andreasen N, Vanmechelen E, Vanderstichele H, Davidsson P, Blennow K. Cerebrospinal fluid levels of total-tau, phosphotau and A beta 42 predicts development of Alzheimer’s disease in patients with mild cognitive impairment. Acta Neurol Scand Suppl 2003, 179: 47–51.

    Article  PubMed  Google Scholar 

  55. Shoji M, Matsubara E, Kanai M, Watanabe M, Nakamura T, Tomidokoro Y, et al. Combination assay of CSF tau, A beta 1–40 and A beta 1–42(43) as a biochemical marker of Alzheimer’s disease. J Neurol Sci 1998, 158: 134–140.

    Article  PubMed  CAS  Google Scholar 

  56. Iqbal K, Alonso AD, Gondal JA, Gong CX, Haque N, Khatoon S, et al. Mechanism of neurofibrillary degeneration and pharmacologic therapeutic approach. J Neural Transm Suppl 2000, 59: 213–222.

    PubMed  CAS  Google Scholar 

  57. Mandelkow EM, Mandelkow E. Tau in Alzheimer’s disease. Trends Cell Biol 1998, 8: 425–427.

    Article  PubMed  CAS  Google Scholar 

  58. Hampel H, Teipel SJ, Fuchsberger T, Andreasen N, Wiltfang J, Otto M, et al. Value of CSF beta-amyloid1-42 and tau as predictors of Alzheimer’s disease in patients with mild cognitive impairment. Mol Psychiatry 2004, 9: 705–710.

    PubMed  CAS  Google Scholar 

  59. 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  PubMed Central  PubMed  CAS  Google Scholar 

  60. Mattsson N, Zetterberg H, Hansson O, Andreasen N, Parnetti L, Jonsson M, et al. CSF biomarkers and incipient Alzheimer disease in patients with mild cognitive impairment. JAMA 2009, 302: 385–393.

    Article  PubMed  CAS  Google Scholar 

  61. 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.

    Article  PubMed  CAS  Google Scholar 

  62. Brys M, Pirraglia E, Rich K, Rolstad S, Mosconi L, Switalski R, et al. Prediction and longitudinal study of CSF biomarkers in mild cognitive impairment. Neurobiol Aging 2009, 30: 682–690.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  63. Itoh N, Arai H, Urakami K, Ishiguro K, Ohno H, Hampel H, et al. Large-scale, multicenter study of cerebrospinal fluid tau protein phosphorylated at serine 199 for the antemortem diagnosis of Alzheimer’s disease. Ann Neurol 2001, 50: 150–156.

    Article  PubMed  CAS  Google Scholar 

  64. Kohnken R, Buerger K, Zinkowski R, Miller C, Kerkman D, DeBernardis J, et al. Detection of tau phosphorylated at threonine 231 in cerebrospinal fluid of Alzheimer’s disease patients. Neurosci Lett 2000, 287: 187–190.

    Article  PubMed  CAS  Google Scholar 

  65. 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  PubMed  Google Scholar 

  66. Hu YY, He SS, Wang XC, Duan QH, Khatoon S, Iqbal K, et al. Elevated levels of phosphorylated neurofilament proteins in cerebrospinal fluid of Alzheimer disease patients. Neurosci Lett 2002, 320: 156–160.

    Article  PubMed  CAS  Google Scholar 

  67. 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  PubMed Central  PubMed  CAS  Google Scholar 

  68. Mulder C, Verwey NA, van der Flier WM, Bouwman FH, Kok A, van Elk EJ, et al. Amyloid-beta(1–42), total tau, and phosphorylated tau as cerebrospinal fluid biomarkers for the diagnosis of Alzheimer disease. Clin Chem 2010, 56: 248–253.

    Article  PubMed  CAS  Google Scholar 

  69. Qin W, Ho L, Wang J, Peskind E, Pasinetti GM. S100A7, a novel Alzheimer’s disease biomarker with non-amyloidogenic alpha-secretase activity acts via selective promotion of ADAM-10. PLoS One 2009, 4: e4183

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  70. Barao S, Zhou LJ, Adamczuk K, Vanhoutvin T, van Leuven F, Demedts D, et al. BACE1 levels correlate with phosphotau levels in human cerebrospinal fluid. Curr Alzheimer Res 2013, 10: 671–678.

    Article  PubMed  CAS  Google Scholar 

  71. Mulder SD, van der Flier WM, Verheijen JH, Mulder C, Scheltens P, Blankenstein MA, et al. BACE1 activity in cerebrospinal fluid and its relation to markers of AD Pathology. J Alzheimers Dis 2010, 20: 253–260.

    PubMed  CAS  Google Scholar 

  72. Gao CM, Yam AY, Wang XM, Magdangal E, Salisbury C, Peretz D, et al. A beta 40 Oligomers identified as a potential biomarker for the diagnosis of Alzheimer’s disease. PLoS One 2010, 5.

  73. Verwey NA, Kester MI, van der Flier WM, Veerhuis R, Berkhof H, Twaalfhoven H, et al. Additional Value of CSF Amyloid-beta(40) Levels in the Differentiation between FTLD and Control Subjects. J Alzheimers Dis 2010, 20: 445–452.

    PubMed  CAS  Google Scholar 

  74. Bibl M, Gallus M, Welge V, Esselmann H, Wolf S, Ruther E, et al. Cerebrospinal fluid amyloid-beta 2–42 is decreased in Alzheimer’s, but not in frontotemporal dementia. J Neural Transm 2012, 119: 805–813.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  75. Ikeuchi T, Hirayama S, Miida T, Fukamachi I, Tokutake T, Ebinuma H, et al. Increased levels of soluble LR11 in cerebrospinal fluid of patients with Alzheimer disease. Dement Geriatr Cogn Disord 2010, 30: 28–32.

    Article  PubMed  CAS  Google Scholar 

  76. Laske C, Stransky E, Hoffmann N, Maetzler W, Straten G, Eschweiler GW, et al. Macrophage colony-stimulating factor (M-CSF) in plasma and CSF of patients with mild cognitive impairment and Alzheimer’s disease. Curr Alzheimer Res 2010, 7: 409–414.

    Article  PubMed  CAS  Google Scholar 

  77. Jiang H, Hampel H, Prvulovic D, Wallin A, Blennow K, Li RN, et al. Elevated CSF levels of TACE activity and soluble TNF receptors in subjects with mild cognitive impairment and patients with Alzheimer’s disease. Mol Neurodegener 2011, 6: 69.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  78. Yin GN, Lee HW, Cho JY, Suk K. Neuronal pentraxin receptor in cerebrospinal fluid as a potential biomarker for neurodegenerative diseases. Brain Res 2009, 1265: 158–170.

    Article  PubMed  CAS  Google Scholar 

  79. Toledo JB, Korff A, Shaw LM, Trojanowski JQ, Zhang J. CSF alpha-synuclein improves diagnostic and prognostic performance of CSF tau and A beta in Alzheimer’s disease. Acta Neuropathol 2013, 126: 683–697.

    Article  PubMed  CAS  Google Scholar 

  80. Santos SM, Garcia-Nimo L, Santos SS, Tavares I, Cocho JA, Castanho M. Neuropeptide kyotorphin (tyrosyl-arginine) has decreased levels in the cerebro-spinal fluid of Alzheimer’sdisease patients: potential diagnostic and pharmacologic alimplications. Front Aging Neurosci 2013, 5.

  81. Montine TJ, Peskind ER, Quinn JF, Wilson AM, Montine KS, Galasko D. Increased cerebrospinal fluid F-2-isoprostanes are associated with aging and latent Alzheimer’s disease as identified by biomarkers. Neuromolecular Med 2011, 13: 37–43.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  82. Correa JD, Starling D, Teixeira AL, Caramelli P, Silva TA. Chemokines in CSF of Alzheimer’s disease patients. Arq Neuropsiquiatr 2011, 69: 455–459.

    Article  PubMed  Google Scholar 

  83. Craig-Schapiro R, Perrin RJ, Roe CM, Xiong CJ, Carter D, Cairns NJ, et al. YKL-40: A novel prognostic fluid biomarker for preclinical Alzheimer’s disease. Biol Psychiatry 2010, 68: 903–912.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  84. Tarawneh R, D’Angelo G, Macy E, Xiong CJ, Carter D, Cairns NJ, et al. Visinin-like Protein-1: diagnostic and prognostic biomarker in Alzheimer disease. Ann Neurol 2011, 70: 274–285.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  85. Tarawneh R, Lee JM, Ladenson JH, Morris JC, Holtzman DM. CSF VILIP-1 predicts rates of cognitive decline in early Alzheimer disease. Neurology 2012, 78: 709–719.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  86. Zenzmaier C, Marksteiner J, Kiefer A, Berger P, Humpel C. Dkk-3 is elevated in CSF and plasma of Alzheimer’s disease patients. J Neurochem 2009, 110: 653–661.

    Article  PubMed  CAS  Google Scholar 

  87. Kosicek M, Kirsch S, Bene R, Trkanjec Z, Titlic M, Bindila L, et al. Nano-HPLC-MS analysis of phospholipids in cerebrospinal fluid of Alzheimer’s disease patients-a pilot study. Anal Bioanal Chem 2010, 398: 2929–2937.

    Article  PubMed  CAS  Google Scholar 

  88. Abraham JD, Calvayrac-Pawlowski S, Cobo S, Salvetat N, Vicat G, Molina L, et al. Combined measurement of PEDF, haptoglobin and tau in cerebrospinal fluid improves the diagnostic discrimination between alzheimer’s disease and other dementias. Biomarkers 2011, 16: 161–171.

    Article  PubMed  CAS  Google Scholar 

  89. Guo LH, Alexopoulos P, Perneczky R. Heart-type fatty acid binding protein and vascular endothelial growth factor: cerebrospinal fluid biomarker candidates for Alzheimer’s disease. Eur Arch Psychiatry Clin Neurosci 2013, 263: 553–560.

    Article  PubMed  Google Scholar 

  90. Vafadar-Isfahani B, Ball G, Coveney C, Lemetre C, Boocock D, Minthon L, et al. Identification of SPARC-like 1 protein as part of a biomarker panel for Alzheimer’s disease in cerebrospinal fluid. J Alzheimers Dis 2012, 28: 625–636.

    PubMed  CAS  Google Scholar 

  91. Perrin RJ, Craig-Schapiro R, Malone JP, Shah AR, Gilmore P, Davis AE, et al. Identification and validation of novel cerebrospinal fluid biomarkers for staging early Alzheimer’s disease. PLoS One 2011, 6: e16032.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  92. Craig-Schapiro R, Kuhn M, Xiong CJ, Pickering EH, Liu JX, Misko TP, et al. Multiplexed immunoassay panel identifies novel CSF biomarkers for Alzheimer’s disease diagnosis and prognosis. PLoS One 2011, 6: e18850.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  93. Jahn H, Wittke S, Zurbig P, Raedler TJ, Arlt S, Kellmann M, et al. Peptide fingerprinting of Alzheimer’s disease in cerebrospinal fluid: identification and prospective evaluation of new synaptic biomarkers. PLoS One 2011, 6: e26540.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Xifei Yang.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sui, X., Liu, J. & Yang, X. Cerebrospinal fluid biomarkers of Alzheimer’s disease. Neurosci. Bull. 30, 233–242 (2014). https://doi.org/10.1007/s12264-013-1412-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12264-013-1412-1

Keywords

Navigation