Home LiteratureArticle Details
PMID: 11831556 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Review

CSF total tau, Abeta42 and phosphorylated tau protein as biomarkers for Alzheimer's disease.

Molecular neurobiology ·Vol. 24 ·No. 1-3 ·2001-00-00 ·Pages 87-97

Blennow K, Vanmechelen E, Hampel H

Abstract

With the arrival of effective symptomatic treatments and the promise of drugs that may delay progression, we now need to identify Alzheimer's disease (AD) at an early stage of the disease. To diagnose AD earlier and more accurately, attention has been directed toward peripheral biochemical markers. This article reviews promising potential cerebrospinal fluid (CSF) biomarkers for AD focussing on their role in clinical diagnosis. In particular, two biochemical markers, CSF total tau (t-tau) protein and the 42 amino acid form of beta-amyloid (Abeta42), perform satisfactorily enough to achieve a role in the clinical diagnostic settings of patients with dementia together with the cumulative information from basic clinical work-up, genetic screening, and brain imaging. These CSF markers are particularly useful to discriminate early or incipient AD from age-associated memory impairment, depression, and some secondary dementias. In order to discriminate AD from other primary dementia disorders, however, more accurate and specific markers are needed. Preliminary evidence strongly suggests that quantification of tau phosphorylated at specific sites in CSF improves early detection, differential diagnosis, and tracking of disease progression in AD.

MeSH Terms
Alzheimer Disease/cerebrospinal fluid,diagnosis Amyloid beta-Peptides/cerebrospinal fluid Biomarkers/cerebrospinal fluid Humans Peptide Fragments/cerebrospinal fluid Phosphorylation Sensitivity and Specificity tau Proteins/cerebrospinal fluid
Chemicals
Amyloid beta-Peptides Biomarkers Peptide Fragments amyloid beta-protein (1-42) tau Proteins
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Blennow K
Department of Clinical Neuroscience, Unit of Neurochemistry, University of Göteborg, Sweden. KAJ.BLENNOW@NEURO.GU.SE
Vanmechelen E
Hampel H
References (68)
68 references, click to expand
  1. 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 Jun;56(6):673-80 PMID: 10369305
  2. The NINCDS-ADRDA Work Group criteria for the clinical diagnosis of probable Alzheimer's disease: a clinicopathologic study of 57 cases.
    Neurology. 1988 Mar;38(3):359-64 PMID: 3347338
  3. Amyloid beta protein 42(43) in cerebrospinal fluid of patients with Alzheimer's disease.
    J Neurol Sci. 1997 May 1;148(1):41-5 PMID: 9125389
  4. Increased cerebrospinal fluid tau in patients with Alzheimer's disease.
    Neurosci Lett. 1995 Feb 17;186(2-3):189-91 PMID: 7777193
  5. No increase in cerebrospinal fluid tau protein levels in patients with vascular dementia.
    Neurosci Lett. 1998 Nov 13;256(3):174-6 PMID: 9855368
  6. Glucose hypometabolism and neuropathological correlates in brains of dementia with Lewy bodies.
    Exp Neurol. 2000 Apr;162(2):247-56 PMID: 10739631
  7. A comparison of tau protein in cerebrospinal fluid between corticobasal degeneration and progressive supranuclear palsy.
    Neurosci Lett. 1999 Jan 8;259(2):127-9 PMID: 10025574
  8. Decreased beta-amyloid1-42 in cerebrospinal fluid of patients with Creutzfeldt-Jakob disease.
    Neurology. 2000 Mar 14;54(5):1099-102 PMID: 10720281
  9. Tau protein in cerebrospinal fluid: a new diagnostic and prognostic marker in Alzheimer disease?
    Alzheimer Dis Assoc Disord. 1998 Sep;12(3):211-4 PMID: 9772026
  10. Consensus report of the Working Group on: "Molecular and Biochemical Markers of Alzheimer's Disease". The Ronald and Nancy Reagan Research Institute of the Alzheimer's Association and the National Institute on Aging Working Group.
    Neurobiol Aging. 1998 Mar-Apr;19(2):109-16 PMID: 9558143
  11. Low frequency of post-lumbar puncture headache in demented patients.
    Acta Neurol Scand. 1993 Sep;88(3):221-3 PMID: 8256560
  12. Detection of tau proteins in normal and Alzheimer's disease cerebrospinal fluid with a sensitive sandwich enzyme-linked immunosorbent assay.
    J Neurochem. 1993 Nov;61(5):1828-34 PMID: 8228996
  13. Improved discrimination of AD patients using beta-amyloid(1-42) and tau levels in CSF.
    Neurology. 1999 May 12;52(8):1555-62 PMID: 10331678
  14. Low cerebrospinal fluid beta-amyloid 42 in patients with acute bacterial meningitis and normalization after treatment.
    Neurosci Lett. 2001 Nov 13;314(1-2):33-6 PMID: 11698140
  15. Cerebrospinal beta-amyloid ((1-42)) in early Alzheimer's disease: association with apolipoprotein E genotype and cognitive decline.
    Neurosci Lett. 2000 Apr 21;284(1-2):85-8 PMID: 10771168
  16. CSF tau is related to apolipoprotein E genotype in early Alzheimer's disease.
    Neurology. 1998 Jan;50(1):169-74 PMID: 9443475
  17. Plasma and cerebrospinal fluid levels of amyloid beta proteins 1-40 and 1-42 in Alzheimer disease.
    Arch Neurol. 2000 Jan;57(1):100-5 PMID: 10634455
  18. Evaluation of CSF-tau and CSF-Abeta42 as diagnostic markers for Alzheimer disease in clinical practice.
    Arch Neurol. 2001 Mar;58(3):373-9 PMID: 11255440
  19. Cerebrospinal fluid A beta42 is increased early in sporadic Alzheimer's disease and declines with disease progression.
    Ann Neurol. 1999 Apr;45(4):504-11 PMID: 10211475
  20. A4 amyloid protein deposition and the diagnosis of Alzheimer's disease: prevalence in aged brains determined by immunocytochemistry compared with conventional neuropathologic techniques.
    Neurology. 1988 Nov;38(11):1688-93 PMID: 3054625
  21. Tau protein in cerebrospinal fluid: a biochemical marker for axonal degeneration in Alzheimer disease?
    Mol Chem Neuropathol. 1995 Dec;26(3):231-45 PMID: 8748926
  22. Elevation of microtubule-associated protein tau in the cerebrospinal fluid of patients with Alzheimer's disease.
    Neurology. 1995 Apr;45(4):788-93 PMID: 7723971
  23. Sensitivity, specificity, and stability of CSF-tau in AD in a community-based patient sample.
    Neurology. 1999 Oct 22;53(7):1488-94 PMID: 10534256
  24. Tracking of Alzheimer's disease progression with cerebrospinal fluid tau protein phosphorylated at threonine 231.
    Ann Neurol. 2001 Apr;49(4):545-6 PMID: 11310639
  25. 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 Jul;55(7):937-45 PMID: 9678311
  26. Mild cognitive impairment: clinical characterization and outcome.
    Arch Neurol. 1999 Mar;56(3):303-8 PMID: 10190820
  27. Decreased CSF amyloid beta42 and normal tau levels in dementia with Lewy bodies.
    Neurology. 2000 May 9;54(9):1875-6 PMID: 10802808
  28. 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 Jul;44(1):17-26 PMID: 9667589
  29. Cerebrospinal fluid tau protein shows a better discrimination in young old (<70 years) than in old old patients with Alzheimer's disease compared with controls.
    Neurosci Lett. 1999 Dec 17;277(1):21-4 PMID: 10643888
  30. Increased tau in the cerebrospinal fluid of patients with frontotemporal dementia and Alzheimer's disease.
    Neurosci Lett. 1999 Jan 8;259(2):133-5 PMID: 10025576
  31. "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician.
    J Psychiatr Res. 1975 Nov;12(3):189-98 PMID: 1202204
  32. Basic and clinical studies on the measurement of tau protein in cerebrospinal fluid as a biological marker for Alzheimer's disease and related disorders: multicenter study in Japan.
    Methods Find Exp Clin Pharmacol. 1998 Apr;20(3):227-35 PMID: 9646285
  33. Combined assessment of tau and neuronal thread protein in Alzheimer's disease CSF.
    Neurology. 2000 Apr 11;54(7):1498-504 PMID: 10751266
  34. Reduction of beta-amyloid peptide42 in the cerebrospinal fluid of patients with Alzheimer's disease.
    Ann Neurol. 1995 Oct;38(4):643-8 PMID: 7574461
  35. Decreased Levels of Amyloid-beta 1-42 in Cerebrospinal Fluid of Creutzfeldt-Jakob Disease Patients.
    J Alzheimers Dis. 1999 Dec;1(6):419-424 PMID: 12214117
  36. Cerebrospinal fluid tau protein levels in demented and nondemented alcoholics.
    Alcohol Clin Exp Res. 1999 Apr;23(4):575-7 PMID: 10235290
  37. Transient increase in total tau but not phospho-tau in human cerebrospinal fluid after acute stroke.
    Neurosci Lett. 2001 Jan 19;297(3):187-90 PMID: 11137759
  38. CSF phosphorylated tau protein and mild cognitive impairment: a prospective study.
    Exp Neurol. 2000 Nov;166(1):201-3 PMID: 11031097
  39. Tau protein and the neurofibrillary pathology of Alzheimer's disease.
    Trends Neurosci. 1993 Nov;16(11):460-5 PMID: 7507619
  40. Cerebrospinal fluid tau levels in neurodegenerative diseases with distinct tau-related pathology.
    Biochem Biophys Res Commun. 1997 Jul 18;236(2):262-4 PMID: 9240421
  41. Detection of tau phosphorylated at threonine 231 in cerebrospinal fluid of Alzheimer's disease patients.
    Neurosci Lett. 2000 Jun 30;287(3):187-90 PMID: 10863026
  42. Apolipoprotein E genotyping and cerebrospinal fluid tau protein: implications for the clinical diagnosis of Alzheimer's disease.
    Gerontology. 1997;43 Suppl 1:2-10 PMID: 9187933
  43. Clinical-neuropathological correlations in Alzheimer's disease and related dementias.
    Arch Neurol. 1994 Sep;51(9):888-95 PMID: 8080388
  44. Tangles and plaques in nondemented aging and "preclinical" Alzheimer's disease.
    Ann Neurol. 1999 Mar;45(3):358-68 PMID: 10072051
  45. Tau protein in cerebrospinal fluid is significantly increased at the earliest clinical stage of Alzheimer disease.
    Alzheimer Dis Assoc Disord. 1998 Dec;12(4):372-7 PMID: 9876968
  46. Assessment of CSF levels of tau protein in mildly demented patients with Alzheimer's disease.
    Neurology. 1997 Mar;48(3):632-5 PMID: 9065538
  47. Cerebrospinal fluid tau and Abeta42 as predictors of development of Alzheimer's disease in patients with mild cognitive impairment.
    Neurosci Lett. 1999 Sep 24;273(1):5-8 PMID: 10505638
  48. Tau protein in cerebrospinal fluid as an aid in the diagnosis of Alzheimer's disease.
    Ann Clin Lab Sci. 1995 May-Jun;25(3):207-17 PMID: 7605102
  49. Both total and phosphorylated tau are increased in Alzheimer's disease.
    J Neurol Neurosurg Psychiatry. 2001 May;70(5):624-30 PMID: 11309456
  50. Total tau protein immunoreactivity in lumbar cerebrospinal fluid of patients with Alzheimer's disease.
    J Neurol Neurosurg Psychiatry. 1996 Feb;60(2):237-8 PMID: 8708672
  51. Elevated levels of tau-protein in cerebrospinal fluid of patients with Creutzfeldt-Jakob disease.
    Neurosci Lett. 1997 Apr 11;225(3):210-2 PMID: 9147407
  52. Analysis of heterogeneous A4 peptides in human cerebrospinal fluid and blood by a newly developed sensitive Western blot assay.
    J Biol Chem. 1996 Sep 13;271(37):22908-14 PMID: 8798471
  53. Diagnostic accuracy of Alzheimer's disease: a clinicopathological study.
    Acta Neuropathol. 1996;91(2):219-20 PMID: 8787159
  54. A population-based study of tau protein and ubiquitin in cerebrospinal fluid in 85-year-olds: relation to severity of dementia and cerebral atrophy, but not to the apolipoprotein E4 allele.
    Neurodegeneration. 1995 Dec;4(4):433-42 PMID: 8846237
  55. Tau protein is a potential biological marker for normal pressure hydrocephalus.
    Psychiatry Clin Neurosci. 2000 Apr;54(2):199-202 PMID: 10803815
  56. Discriminant power of combined cerebrospinal fluid tau protein and of the soluble interleukin-6 receptor complex in the diagnosis of Alzheimer's disease.
    Brain Res. 1999 Mar 27;823(1-2):104-12 PMID: 10095017
  57. Cerebrospinal protein tau is elevated in early Alzheimer's disease.
    Neurosci Lett. 1996 Jul 19;212(3):209-11 PMID: 8843109
  58. Quantification of tau phosphorylated at threonine 181 in human cerebrospinal fluid: a sandwich ELISA with a synthetic phosphopeptide for standardization.
    Neurosci Lett. 2000 May 5;285(1):49-52 PMID: 10788705
  59. Increased CSF tau protein in corticobasal degeneration.
    J Neurol. 1998 Jan;245(1):44-6 PMID: 9457628
  60. Cerebrospinal fluid markers for Alzheimer's disease evaluated after acute ischemic stroke.
    J Alzheimers Dis. 2000 Nov;2(3-4):199-206 PMID: 12214084
  61. Diagnostic accuracy of Alzheimer's disease: a neuropathological study.
    Acta Neuropathol. 1996;91(2):185-93 PMID: 8787153
  62. Update on the dementia spectrum of depression.
    Am J Psychiatry. 1992 Mar;149(3):305-17 PMID: 1536267
  63. Phosphorylated tau in human cerebrospinal fluid is a diagnostic marker for Alzheimer's disease.
    Neurosci Lett. 1999 Jul 30;270(2):91-4 PMID: 10462105
  64. Tau in cerebrospinal fluids: establishment of the sandwich ELISA with antibody specific to the repeat sequence in tau.
    Neurosci Lett. 1995 Feb 17;186(2-3):181-3 PMID: 7777192
  65. CSF levels of tau, beta-amyloid(1-42) and GAP-43 in frontotemporal dementia, other types of dementia and normal aging.
    J Neural Transm (Vienna). 2000;107(5):563-79 PMID: 11072752
  66. 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 Jul;34(7):939-44 PMID: 6610841
  67. Tau and apo E in CSF: potential aid for discriminating Alzheimer's disease from other dementias.
    Neuroreport. 1999 Nov 26;10(17):3491-5 PMID: 10619631
  68. Cerebrospinal fluid tau protein as a biochemical marker for Alzheimer's disease: a community based follow up study.
    J Neurol Neurosurg Psychiatry. 1998 Mar;64(3):298-305 PMID: 9527138
Article Info
Journal
Molecular neurobiology
Abbr.
Mol Neurobiol
ISSN
0893-7648
Published
2001-00-00
Pages
87-97
Language
English
Region
United States
NLM ID
8900963
Subset
IM
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com