Advertisement

Cerebrospinal fluid levels of Aβ42 and tau: potential markers of Alzheimer’s disease

  • D. Galasko
Part of the Journal of Neural Transmission. Supplementa book series (NEURAL SUPPL, volume 53)

Summary

CSF levels of proteins related to the lesions of Alzheimer’s Disease (AD) may be informative. These include the microtubule-associated protein tau, an integral component of neurofibrillary tangles, and Aβ, a 4kDa protein that accumulates in senile plaque amyloid. Many studies have found that CSF tau is increased in AD compared to normal controls (NC). CSF tau may be increased in a minority of patients with destructive neurological disorders or several neurodegenerative conditions, making its use in differential diagnosis less clear. CSF tau consists of fragments that lack extensive phosphorylation. CSF levels of Aβ species ending at residue 40 are unchanged in AD. However species ending at residue 42 (Aβ42) are significantly decreased in AD compared to NC. Decreased Aβ42 may be found in patients with other dementias, some of whom may harbor AD pathology. Simultaneous measurement of CSF Aβ42 and tau may improve discrimination between AD and NC, and may facilitate the diagnosis of early stage AD.

Keywords

Amyotrophic Lateral Sclerosis Amyloid Protein Precursor Vascular Dementia Progressive Supranuclear Palsy Lewy Body Dementia 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Arai H, Terajima M, Miura M, Higuchi S, Muramatsu T, Machida N, Seiki H, Takase S, Clark CM, Lee VM-Y, Trojanowski JQ, Sasaki A (1995) Tau in cerebrospinal fluid: a potential diagnostic marker in Alzheimer’s disease. Ann Neurol 38: 649–652PubMedCrossRefGoogle Scholar
  2. Blennow K, Wallin A, Agren H, Spenger C, Siegfried J, Vanmechelen E (1995) Tau protein in cerebrospinal fluid. A biochemical marker for axonal degeneration in Alzheimer disease? Molec Chem Neuropathol 26: 231–245CrossRefGoogle Scholar
  3. Brioni A, Decker M (1997) Pharmacological treatment of Alzheimer’s disease: molecular and neurobiological foundations, Wiley-Liss, New York, pp 345–366Google Scholar
  4. Cummings BJ, Cottman CW (1995) Image analysis of β-amyloid load in Alzheimer’s disease and relation to dementia severity. Lancet 346: 1524–1528PubMedCrossRefGoogle Scholar
  5. Dickson DW (1997) The pathogenesis of senile plaques. J Neuropathol Exp Neurol 56: 321–339PubMedCrossRefGoogle Scholar
  6. Feany D, Dickson D (1996) Neurodegenerative disorders with extensive tau pathology: a comparative study and review. Ann Neurol 40: 139–148PubMedCrossRefGoogle Scholar
  7. Galasko D, Hansen LA, Katzman R, Wiederholt W, Masliah E, Terry R, Hill LR, Lessin P, Thal LJ (1994) Clinical-neuropathological correlations in Alzheimer’s disease and related dementias. Arch Neurol 51: 888–895PubMedCrossRefGoogle Scholar
  8. Galasko D, Clark C, Chang L, Miller B, Green RC, Motter R, Seubert P (1997) Assessment of cerebrospinal fluid levels of tau in mildly demented patients with Alzheimer’s disease. Neurology 48: 632–635PubMedCrossRefGoogle Scholar
  9. Goedert M (1993) Tau protein and the neurofibrillary pathology of Alzheimer’s disease. Trends Neurosci 16: 460–465, 1993PubMedCrossRefGoogle Scholar
  10. Goedert M, Spillantini MG, Cairns NJ, Crowther RA (1992) Tau proteins of Alzheimer paired helical filaments: abnormal phosphorylation of all six brain isoforms. Neuron 8: 159–168PubMedCrossRefGoogle Scholar
  11. Goedert M, Jakes R, Spillantini MG, Hasegawa M, Smith MJ, Crowther RA (1996) Assembly of microtubule-associated protein tau into Alzheimer-like filaments induced by sulphated glycosaminoglycans. Nature 383: 550–553PubMedCrossRefGoogle Scholar
  12. Hardy J (1997) Amyloid, the presenilins, and Alzheimer’s disease. Trends Neurosci 20: 154–159PubMedCrossRefGoogle Scholar
  13. Ida N, Hartman T, Pantel T, Schroder J, Zerfass R, Forstl H, Sandbrink R, Masters CL, Beyreuther K (1996) Analysis of heterogeneous βA4 peptides in human cerebrospinal fluid by a newly developed sensitive Western blot assay. J Biol Chem 271: 22908–22914PubMedCrossRefGoogle Scholar
  14. Isoe K, Urakami K, Shimomura T, Wakutani Y, Ji Y, Adachi Y, Takahashi K (1996) Tau proteins in cerebrospinal fluid from patients with Alzheimer’s disease: a longitudinal study. Dementia 7: 175–176PubMedGoogle Scholar
  15. Jellinger K, Danielczyk W, Fischer P, Gabriel E (1990) Clinicopathological analysis of dementia disorders in the elderly. J Neurol Sci 95: 239–258PubMedCrossRefGoogle Scholar
  16. Jensen M, Basun H, Lannfelt L (1995) Increased cerebrospinal fluid tau in patients with Alzheimer’s disease. Neurosci Lett 186: 189–191PubMedCrossRefGoogle Scholar
  17. Johnson GV, Seubert P, Cox TM, Motter R, Brown JP, Galasko D (1997) The tau protein in human cerebrospinal fluid is Alzheimer’s disease consists of proteolytically derived fragments. J Neurochem 68: 430–433PubMedCrossRefGoogle Scholar
  18. Kanai M, Matsubara E, Igeta Y, Tomidokoro K, Ishiguro T, Kawarabayashi T, Watanabe M, Shizuka M, Nakamura T, Okamoto K, Hirai S, Shoji M (1996) Cerebrospinal fluid tau and beta-amyloid 1–40/42 in Alzheimer’s disease. Soc Neurosci Abstr 22: 1169Google Scholar
  19. Klatka LA, Schiffer RB, Powers JM, Kazee AM (1996) Incorrect diagnosis of Alzheimer’s disease. A clinicopathologic study. Arch Neurol 53: 35–42CrossRefGoogle Scholar
  20. McKhann G, Drachman D, Folstein MF, Katzman R, Price D, Stadlan EM (1984) 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 34: 939–944PubMedCrossRefGoogle Scholar
  21. Mori H, Hosoda K, Matsubara E, Nakamoto T, Furiya Y, Endoh R, Usami M, Shoji M, Maruyama S, Hirai S (1995) Tau in cerebrospinal fluids: establishment of the sandwich ELISA with antibody specific to the repeat sequence in tau. Neurosci Lett 186: 181–183PubMedCrossRefGoogle Scholar
  22. Motter R, Vigo-Pelfrey C, Kholodenko D, Barbour R, Johnson-Wood K, Galasko D, Chang L, Miller B, Clark C, Gren R, Olson D, Southwick P, Wolfert R, Munroe B, Lieberburg I, Seubert P, Schenk D (1995) Reduction of β-Amyloid peptide42 in the cerebrospinal fluid of patients with Alzheimer’s disease. Ann Neurol 38: 643–648PubMedCrossRefGoogle Scholar
  23. Nakamura T, Shoji M, Harigaya Y, Watanabe M, Hosoda K, Cheung TT, Shaffer LM, Golde TE, Younkin LH, Younkin SG, Hirai S (1994) Amyloid β protein levels in cerebrospinal fluid are elevated in early-onset Alzheimer’s disease. Ann Neurol 36: 903–911PubMedCrossRefGoogle Scholar
  24. Otto M, Wiltfang J, Tumani H, Zerr I, Lautsch M, Kornhuber J, Weber T, Kretschmer HA, Poser S (1997) Elevated levels of tau-protein in cerebrospinal fluid of patients with Creutzfeldt-Jakob disease. Neurosci Lett 225: 210–212PubMedCrossRefGoogle Scholar
  25. Riemenschneider NM, Buch K, Schmolke M, Kurz A, Guder WG (1996) Cerebrospinal fluid tau is elevated in early Alzheimer’s disease. Neurosci Lett 212: 209–211PubMedCrossRefGoogle Scholar
  26. Rösier N, Wichart I, Jellinger KA (1996) Total tau protein immunoreactivity in lumbar cerebrospinal fluid of patients with Alzheimer’s disease. J Neurol Neurosurg Psychiatry 60: 237–238Google Scholar
  27. Saunders AM, Strittmatter WJ, Schmechel D, et al (1993) Association of apolipoprotein E allele e4 with late-onset familial and sporadic Alzheimer’s disease. Neurology 43: 1467–1472PubMedCrossRefGoogle Scholar
  28. Scheuner D, Eckman C, Jensen M, Song X, Citron M, Suzuki N, Bird TD, Hardy J, Hutton M, Kukull W, Larson E, Levy-Lahad E, Viitanen M, Peskind E, Poorkaj P, Schellenberg G, Tanzi R, Wasco W, Lannfelt L, Selkoe D, Younkin S (1996) Secreted amyloid β-protein similar to that in the senile plaques of Alzheimer’s disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer’s disease. Nature Med 2: 864–870PubMedCrossRefGoogle Scholar
  29. Selkoe DJ (1994) Alzheimer’s disease: a central role for amyloid. J Neuropathol Exp Neurol 53: 438–447PubMedCrossRefGoogle Scholar
  30. Selkoe DJ (1996) Amyloid β-protein and the genetics of Alzheimer’s disease. J Biol Chem 271: 18295–18298PubMedGoogle Scholar
  31. Seubert P, Motter R, Schenk D, Lieberburg I, Kholodenko D, Galasko D, Thomas R, Chang L, Miller B, Clark C, Knopman D, Kaye J, Green RC, Kertiles M, Bashirzadeh R, Boss M (1998) APOE genotype influences the CSF level of Aβ42 in Alzheimer’s disease (in preparation)Google Scholar
  32. Strittmatter WJ, Roses AD (1995) Apolipoprotein E and Alzheimer disease. Proc Natl Acad Sci (USA) 92: 4725–4727CrossRefGoogle Scholar
  33. Strittmatter WJ, Saunders AM, Schmechel D, Pericak-Vance M, Enghild J, Salvesen GS, Roses (1993) Apolipoprotein E: high-avidity binding to β-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proc Natl Acad Sci USA 90: 980–984CrossRefGoogle Scholar
  34. Tamaoka A, Sawamura N, Fukushima T, Shoji S, Matsubara E, Shoji M, Hirai S, Furiya Y, Endoh H, Mori H (1997) Amyloid β protein 42(43) in cerebrospinal fluid of patients with Alzheimer’s disease. J Neurol Sci 148: 4–45CrossRefGoogle Scholar
  35. Trojanowski JQ, Lee VM-Y (1994) Phosphorylation of neuronal cytoskeletal proteins in Alzheimer’s disease and Lewy body dementias. Ann NY Acad Sci 747: 92–109PubMedCrossRefGoogle Scholar
  36. Van Gool WA, Bolhuis PA (1991) Cerebrospinal fluid markers of Alzheimer’s disease. JAGS 39: 1025–1039Google Scholar
  37. Van Gool WA, Kuiper MA, Walstra GJM, Wolters E Ch, Bolhuis PA (1995) Concentrations of amyloid β protein in cerebrospinal fluid of patients with Alzheimer’s disease. Ann Neurol 37: 277–279PubMedCrossRefGoogle Scholar
  38. Vandermeeren M, Mercken M, Vanmechelen E, Six J, Van de Voorde A, Martin J-J, Cras P (1993) Detection of tau proteins in normal and Alzheimer’s disease cerebrospinal fluid with a sensitive sandwich enzyme-linked immunosorbent assay. J Neurochem 61: 1828–1834PubMedCrossRefGoogle Scholar
  39. Vigo-Pelfrey C, Le D, Keim P, Lieberburg I, Schenk DB (1993) Characterization of beta-amyloid peptide from human cerebrospinal fluid. J Neurochem 61: 1965–1968PubMedCrossRefGoogle Scholar
  40. Vigo-Pelfrey C, Seubert P, Barbour R, Blomquist C, Lee M, Lee D, Coria F, Chang L, Miller B, Lieberburg I, Schenk D (1995) Elevation of micro-tubule-associated protein tau in the cerebrospinal fluid of Alzheimer’s patients. Neurology 45: 788–793PubMedCrossRefGoogle Scholar
  41. Wolozin B, Davies P (1987) Alzheimer-related neuronal protein A68: specificity and distribution. Ann Neurol 22: 521–526, 1987PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 1998

Authors and Affiliations

  • D. Galasko
    • 1
    • 2
  1. 1.Department of Neurosciences (Neurology)University of California, and Veterans Affairs Medical CenterSan DiegoUSA
  2. 2.Department of NeurosciencesUniversity of CaliforniaSan DiegoUSA

Personalised recommendations