Clinical significance of neurobiochemical profiles in the lumbar cerebrospinal fluid of Alzheimer’s disease patients

  • N. Rösler
  • I. Wichart
  • K. A. Jellinger


Immunoreactivities of total apolipoprotein E (ApoE-IR), amyloid β peptide (1–42) (Aβ42-IR), interleukin-6 (IL-6-IR), substance P (SPIR) and total τ protein (TTIR) were measured in lumbar cerebrospinal fluid samples of patients with Alzheimer’s disease (AD), non-Alzheimer’s dementias (NAD), neurological disorders without cognitive impairment (OND) and controls without central nervous system disease using sensitive and specific enzyme immunoassay methods. TTIR was highly significantly increased (P<0,001) and Aβ42-IR was significantly decreased (P<0,001 vs. OND/CO, P<0,03 vs. NAD) in the AD cohort compared with the other diagnostic groups. Significant increases in AD were also found for ApoE-IR (P<0,001) and IL-6 (P<0,03), but there was a considerable overlap between groups. In the total AD cohort, SPIR was not significantly changed, but AD patients with late disease onset (τ;65 years) showed significantly higher values than both early onset patients (<65 years) and controls (P<0,05). Discriminant function analysis showed that Aβ42-IR (cut-off value 375pg/ml) and TTIR (cut-off value 440pg/ml) levels contributed most to the group classification of patients. At 85% sensitivity for AD and 100% specificity for controls, the combined evaluation of Aβ42-IR and TTIR in this cross-sectional study resulted in a graph separating AD from non-AD patients with increased specificity of 91% and 75% for AD versus OND and NAD, respectively.


Cerebrospinal fluid neurochemical profiles Alzheimer’s disease apolipoprotein E amyloid β peptide interleukin-6 substance P τprotein 


  1. Andreasen N, Hesse C, Davidsson P, Minthon L, Wallin A, Winblad B, Vanderstichele H, Vanmechelen E, Blennow K (1999a) Cerebrospinal fluid β-amyloid(1–42) in Alzheimer disease: differences between early- and late-onset Alzheimer disease and stability during the course of disease. Arch Neurol 56: 673–680PubMedCrossRefGoogle Scholar
  2. Andreasen N, Minthon L, Vanmechelen E, Vanderstichele H, Davidsson P, Winblad B, Blennow K (1999b) Cerebrospinal fluid tau and Aβ42 as predictors of development of Alzheimer’s disease in patients with mild cognitive impairment. Neurosci Lett 273: 5–8PubMedCrossRefGoogle Scholar
  3. Arai H, Higuchi S, Sasaki H (1997) Apolipoprotein E genotyping and cerebrospinal fluid tau protein: implications for the clinical diagnosis of Alzheimer’s disease. Gerontology 43 [Suppl] 1: 2–10PubMedGoogle Scholar
  4. Bancher C, Jellinger K, Wichart I (1998) Biological markers for the diagnosis of Alzheimer’s disease. J Neural Transm [Suppl] 53: 185–197Google Scholar
  5. Bauer J, Strauss S, Schreiter-Gasser U, Ganter U, Schlegel P, Witt I, Volk B, Berger M (1991) Interleukin-6 and α2-macroglobulin indicate an acute-phase state in Alzheimer’s disease cortices. FEBS Lett 285: 111–114PubMedCrossRefGoogle Scholar
  6. Blacker D, Tanzi RE (1998) The genetics of Alzheimer’s disease – current status and future prospects. Arch Neurol 55: 294–296PubMedCrossRefGoogle Scholar
  7. Blennow K, Vanmechelen E (1998) Combination of the different biological markers for increasing specificity of in vivo Alzheimer’s testing. J Neural Transm [Suppl] 53: 223–235Google Scholar
  8. Blennow K, Wallin A, Davidsson P, Fredman P, Gottfries CG, Svennerholm L (1990) Intra-blood-brain-barrier synthesis of immunoglobulins in patients with dementia of the Alzheimer type. Alzheimer Dis Assoc Disord 4: 79–86PubMedGoogle Scholar
  9. Blennow K, Hesse C, Fredman P (1994) Cerebrospinal fluid apolipoprotein E is reduced in Alzheimer’s disease. Neuroreport 5: 2534–2536PubMedCrossRefGoogle Scholar
  10. Blum-Degen D, Müller T, Kuhn W, Gerlach M, Przuntek H, Riederer P (1995) Interleukin-1β and interleukin-6 are elevated in the cerebrospinal fluid of Alzheimer’s and de novo Parkinson’s disease patients. Neurosci Lett 202: 17–20PubMedCrossRefGoogle Scholar
  11. Campbell IL, Abraham CR, Masliah E, Kemper P, Inglis JD, Oldstone MBA, Mucke L (1993) Neurologic disease induced in transgenic mice by cerebral overexpression of interleukin-6. Proc Natl Acad Sci USA 90: 10061–10065PubMedCrossRefGoogle Scholar
  12. Carlsson J, Armstrong VW, Reiber H, Felgenhauer K, Seidel D (1991) Clinical relevance of the quantification of apolipoprotein E in cerebrospinal fluid. Clin Chim Acta 196: 167–176PubMedCrossRefGoogle Scholar
  13. Consensus Report of the Working Group on: “Molecular and Biochemical Markers of Alzheimer’s Disease” (1998) Neurobiol Aging 19: 109–116CrossRefGoogle Scholar
  14. Corder EH, Lannfelt L, Bogdanovic N, Fratiglioni L, Mori H (1998) The role of apoe polymorphisms in late-onset dementias. Cell Molec Life Sci 54: 928–934PubMedCrossRefGoogle Scholar
  15. Cramer H, Schaudt D, Rissler K, Strubel D, Warter JM, Kuntzmann F (1985) Somatostatin-like immunoreactivity and substance P-like immunoreactivity in the CSF of patients with senile dementia of Alzheimer type, multi-infarct syndrome and communicating hydrocephalus. J Neurol 232: 346–351PubMedCrossRefGoogle Scholar
  16. Dickson DW (1997) The pathogenesis of senile plaques. J Neuropathol Exp Neurol 56: 321–329PubMedCrossRefGoogle Scholar
  17. Engelborghs S, De Brabander M, De Cree J, D’Hooge R, Geerts H, Verhaegen H, De Deyn PP (1999) Unchanged levels of interleukins, neopterin, interferon-γ and tumor necrosis factor-α in cerebrospinal fluid of patients with dementia of the Alzheimer type. Neurochem Int 34: 523–530PubMedCrossRefGoogle Scholar
  18. Fishman RA (1992) Cerebrospinal fluid in diseases of the nervous system, 2nd edn. Saunders, Philadelphia, p 339Google Scholar
  19. Folstein MF, Folstein SE, McHugh PR (1975) “Mini mental state”: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12: 189–198PubMedCrossRefGoogle Scholar
  20. Frei K, Malipiero UV, Leist TP, Zinkernagel RM, Schwab ME, Fontana A (1989) On the cellular source and function of interleukin-6 produced in the central nervous system in viral diseases. Eur J Immunol 19: 689–694PubMedCrossRefGoogle Scholar
  21. Frölich L, Kornhuber J, Ihl R, Fritze J, Maurer K, Riederer P (1991) Integrity of the blood-CSF barrier in dementia of Alzheimer type: CSF/serum ratios of albumin and IgG. Eur Arch Psychiatry Clin Neurosci 240: 363–366PubMedCrossRefGoogle Scholar
  22. Fukuyama R, Mizuno T, Mori S, Yanagisawa K, Nakajima K, Fushiki S (2000) Age-dependent decline in the apolipoprotein E level in cerebrospinal fluid from control subjects and its increase in cerebrospinal fluid from patients with Alzheimer’s disease. Eur Neurol 43: 161–169PubMedCrossRefGoogle Scholar
  23. Gahtan E, Overmier JB (1999) Inflammatory pathogenesis in Alzheimer’s disease: biological mechanisms and cognitive sequeli. Neurosci Biobehav Rev 23: 615–633PubMedCrossRefGoogle Scholar
  24. Galasko D (1998) Cerebrospinal fluid levels of Aβ42 and tau: potential markers of Alzheimer’s disease. J Neural Transm [Suppl] 53: 209–221Google Scholar
  25. Galasko D, Chang L, Motter R, Clark CM, Kaye J, Knopman D, Thomas R, Kholodenko D, Schenk D, Lieberburg I, Miller B, Green R, Basherad R, Kertiles L, Boss MA, Seubert P (1998) High cerebrospinal fluid tau and low amyloid β42 levels in the clinical diagnosis of Alzheimer disease and relation to apolipoprotein E genotype. Arch Neurol 55: 937–945PubMedCrossRefGoogle Scholar
  26. Gitter BD, Regoli D, Howbert JJ, Glasebrook AL, Waters DC (1994) Interleukin-6 secretion from human astrocytoma cells induced by substance P. J Neuroimmunol 51: 101–108PubMedCrossRefGoogle Scholar
  27. Goedert M (1993) Tau protein and the neurofibrillary pathology of Alzheimer’s disease. Trends Neurosci 16: 460–465PubMedCrossRefGoogle Scholar
  28. Green AJ, Harvey RJ, Thompson EJ, Rossor MN (1999) Increased tau in the cerebrospinal fluid of patients with frontotemporal dementia and Alzheimer’s disease. Neurosci Lett 259: 133–135PubMedCrossRefGoogle Scholar
  29. Gsell W, Strein I, Krause U, Riederer P (1997) Neurochemical abnormalities in Alzheimer’s disease and Parkinson’s disease — a comparative review. J Neural Transm [Suppl] 51: 145–159Google Scholar
  30. Hahne S, Nordstedt C, Ahlin A, Nybäck H (1997) Levels of cerebrospinal fluid apolipoprotein E in patients with Alzheimer’s disease and healthy controls. Neurosci Lett 224: 99–102PubMedCrossRefGoogle Scholar
  31. Hama T, Kushima Y, Miyamoto M, Kubota M, Takei N, Hatanaka H (1991) Interleukin-6 improves the survival of mesencephalic catecholaminergic and septal cholinergic neurons. Neuroscience 40: 445–452PubMedCrossRefGoogle Scholar
  32. Hampel H, Schoen D, Schwarz MJ, Kötter HU, Schneider C, Sunderland T, Dukoff R, Levy J, Padberg F, Stubner S, Buch K, Müller N, Möller HJ (1997) Interleukin-6 is not altered in cerebrospinal fluid of first-degree relatives and patients with Alzheimer’s disease. Neurosci Lett 228: 143–146PubMedCrossRefGoogle Scholar
  33. Hampel H, Kötter HU, Padberg F, Körschenhausen DA, Möller HJ (1999) Oligoclonal bands and blood-cerebrospinal fluid barrier dysfunction in a subset of patients with Alzheimer disease: comparison with vascular dementia, major depression, and multiple sclerosis. Alzheimer Dis Assoc Disord 13: 9–19PubMedCrossRefGoogle Scholar
  34. Hesse C, Larsson H, Fredman P, Minthon L, Andreason N, Davidsson P, Blennow K (2000) Measurement of apolipoprotein E (apoE) in cerebrospinal fluid. Neurochem Res 25: 511–517PubMedCrossRefGoogle Scholar
  35. Flock C, Golombowski S, Naser W, Müller-Spahn F (1995) Increased levels of tau protein in cerebrospinal fluid of patients with Alzheimer’s disease – correlation with degree of cognitive impairment. Ann Neurol 37: 414–415Google Scholar
  36. Hüll M, Strauss S, Volk B, Berger M, Bauer J (1995) Interleukin-6 is present in early stages of plaque formation and is restricted to the brains of Alzheimer’s disease patients. Acta Neuropathol 89: 544–551CrossRefGoogle Scholar
  37. Hulstaert F, Blennow K, Ivanoiu A, Schoonderwaldt HC, Riemenschneider M, De Deyn PP, Bancher C, Cras P, Wiltfang J, Mehta PD, Iqbal K, Pottel H, Vanmechelen E, Vanderstichele H (1999) Improved discrimination of Alzheimer’s disease patients using β-amyloid(1–42) and tau levels in CSF. Neurology 52: 1555–1562PubMedGoogle Scholar
  38. Ishiguro K, Ohno H, Arai H, Yamaguchi H, Urakami K, Park JM, Sato K, Kohno H, Imahori K (1999) Phosphorylated tau in human cerebrospinal fluid is a diagnostic marker for Alzheimer’s disease. Neurosci Lett 270: 91–94PubMedCrossRefGoogle Scholar
  39. Jellinger KA (1998) The neuropathological diagnosis of Alzheimer disease. J Neural Transm [Suppl] 53: 97–118Google Scholar
  40. Jellinger KA (1999) What is new in degenerative dementia disorders? Wien Klin Wochenschr 111: 682–704PubMedGoogle Scholar
  41. Kahle PJ, Jakowec M, Teipel SH, Hampel H, Pethinger GM, Di Monte DA, Silverberg GD, Möller HJ, Yesavage JA, Trinklenberg JR, Shooter EM, Murphy GM (2000) Combined assessment of tau and neuronal thread protein in Alzheimer’s disease CSF. Neurology 54: 1498–1504PubMedGoogle Scholar
  42. Kanai M, Matsubara E, Isoe K, Urakami K, Nakashima K, Arai H, Sasaki H, Abe K, Iwatsubo T, Kosaka T, Watanabe M, Tomidokoro Y, Shizuka M, Mizushima K, Nakamura T, Igeta Y, Ikeda Y, Amari M, Kawarabayashi T, Ishiguro K, Harigaya Y, Wakabayashi K, Okamoto K, Hirai S, Shoji M (1998) Longitudinal study of cerebrospinal fluid levels of tau, Aβ(1–40), and Aβ(1–42)(43) in Alzheimer’s disease: a study in Japan. Ann Neurol 44: 17–26PubMedCrossRefGoogle Scholar
  43. Kay AD, May C, Papadopoulos NM, Costello R, Atack JR, Luxenberg JS, Cutler NR, Rapoport SI (1987) CSF and serum concentrations of albumin and IgG in Alzheimer’s disease. Neurobiol Aging 8: 21–25PubMedCrossRefGoogle Scholar
  44. Kowall NW, Beal MF, Busciglio J, Duffy LK, Yankner BA (1991) An in vivo model for the neurodegenerative effects of β amyloid and protection by substance P. Proc Natl Acad Sci USA 88: 7247–7251PubMedCrossRefGoogle Scholar
  45. Lanzrein AS, Johnston CM, Perry VH, Jobst KA, King EM, Smith AD (1998) Longitudinal study of inflammatory factors in serum, cerebrospinal fluid, and brain tissue in Alzheimer disease: interleukin-1β, interleukin-6, interleukin-1 receptor antagonist, tumor necrosis factor-α, the soluble tumor necrosis factor receptors I and II, and α1-antichymotrypsin. Alzheimer Dis Assoc Disord 12: 215–227PubMedCrossRefGoogle Scholar
  46. Lefranc D, Vermersch P, Dallongeville J, Daems-Monpeurt C, Petit H, Delacourte A (1996) Relevance of the quantification of apolipoprotein E in the cerebrospinal fluid in Alzheimer’s disease. Neurosci Lett 212: 91–94PubMedCrossRefGoogle Scholar
  47. Leonardi A, Gandolfo C, Caponnetto C, Arata L, Vecchia R (1985) The integrity of the blood-brain barrier in Alzheimer’s type and multi-infarct dementia evaluated by the study of albumin and IgG in serum and cerebrospinal fluid. J Neurol Sci 67: 253–261PubMedCrossRefGoogle Scholar
  48. Lindh M, Blomberg M, Jensen M, Basun H, Lannfelt L, Engvall B, Scharnagl H, März W, Wahlund LO, Cowburn RF (1997) Cerebrospinal fluid apolipoprotein E (apoE) levels in Alzheimer’s disease patients are increased at follow up and show a correlation with levels of tau protein. Neurosci Lett 229: 85–88CrossRefGoogle Scholar
  49. Malek-Ahmadi P (1992) Substance P and neuropsychiatry disorders: an overview. Neurosci Biobehav Rev 16: 365–369PubMedCrossRefGoogle Scholar
  50. Martinez M, Frank A, Hernanz A (1993) Relationship of interleukin-1β and β2-microglobulin with neuropeptides in cerebrospinal fluid of patients with dementia of the Alzheimer type. J Neuroimmunol 48: 235–240PubMedCrossRefGoogle Scholar
  51. März P, Heese K, Hock C, Golombowksi S, Müller-Spahn F, Rose-John S, Otten U (1997) Interleukin-6 (IL-6) and soluble forms of IL-6 receptors are not altered in cerebrospinal fluid of Alzheimer’s disease patients. Neurosci Lett 239: 29–32PubMedCrossRefGoogle Scholar
  52. Mayeux R, Saunders AM, Shea S, Mirra S, Evans D, Roses AD, Hyman BT, Grain B, Tang MX, Phelps CH (1998) Utility of the apolipoprotein E genotype in the diagnosis of Alzheimer’s disease. N Engl J Med 338: 506–511PubMedCrossRefGoogle Scholar
  53. McGeer PL, Rogers J, McGeer EG (1994) Neuroimmune mechanisms in Alzheimer disease pathogenesis. Alzheimer Dis Assoc Disord 8: 149–158PubMedCrossRefGoogle Scholar
  54. McKhann G, Drachman D, Folstein M, 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: 939–944PubMedGoogle Scholar
  55. Mecocci P, Parnetti L, Reboldi GP, Santucci C, Gaiti A, Ferri C, Gernini I, Romagnoli M, Cadini D, Senin U (1991) Blood-brain-barrier in a geriatric population: barrier function in degenerative and vascular dementias. Acta Neurol Scand 84: 210–213PubMedCrossRefGoogle Scholar
  56. Merched A, Blain H, Visvikis S, Herbeth B, Jeandel C, Siest G (1997) Cerebrospinal fluid apolipoprotein E level is increased in late-onset Alzheimer’s disease. J Neurol Sci 145: 33–39PubMedCrossRefGoogle Scholar
  57. Motter R, Vigo-Pelfrey C, Kholodenko D, Barbour R, Johnson-Wood K, Galasko D, Chang L, Miller B, Clark C, Green 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
  58. Nagy Z, Esiri MM, Hindley NJ, Joachim C, Morris JH, King EM, McDonald B, Litchfield S, Barnetson L, Jobst KA, Smith AD (1998) Accuracy of clinical operational diagnostic criteria for Alzheimer’s disease in relation to different pathological diagnostic protocols. Dement Geriatr Cogn Disord 9: 219–226PubMedCrossRefGoogle Scholar
  59. Namba Y, Tomanaga M, Kawasaki H, Otomo E, Ikeda K (1991) Apolipoprotein E immunoreactivity in cerebral amyloid deposits and neurofibrillary tangles in Alzheimer’s disease and kuru plaque amyloid in Creutzfeldt-Jakob disease. Brain Res 541: 163–166PubMedCrossRefGoogle Scholar
  60. Nijsten MW, de Groot ER, ten Duis HJ, Klasen HJ, Hack CE, Aarden LA (1987) Serum levels of interleukin-6 and acute phase response. Lancet ii: 921CrossRefGoogle Scholar
  61. Pirttilä T, Mehta PD, Soininen H, Kim KS, Heinonen O, Paljärvi L, Kosunen O, Riekkinen P, Wisniewski HM (1996) Cerebrospinal fluid concentrations of soluble amyloid β-protein and apolipoprotein E in patients with Alzheimer’s disease: correlations with amyloid load in the brain. Arch Neurol 53: 189–193PubMedGoogle Scholar
  62. Pokier J (1994) Apolipoprotein E in animal models of CNS injury and in Alzheimer’s disease. Trends Neurosci 17: 525–530CrossRefGoogle Scholar
  63. Reiber H, Felgenhauer K (1987) Protein transfer at the blood cerebrospinal fluid barrier and the quantitation of the humoral immune response within the central nervous system.. Clin Chim Acta 163: 319–328PubMedCrossRefGoogle Scholar
  64. Rösier N, Wichart I, Jellinger KA (1996a) Intra vitam lumbar cerebrospinal fluid and serum and postmortem ventricular immunoreactive apolipoprotein E in patients with Alzheimer’s disease. J Neurol Neurosurg Psychiatry 60: 452–454CrossRefGoogle Scholar
  65. Rösier N, Wichart I, Jellinger KA (1996b) Total tau protein immunoreactivity in lumbar cerebrospinal fluid of patients with Alzheimer’s disease. J Neurol Neurosurg Psychiatry 60: 237–238Google Scholar
  66. Samuels SC, Silverman JM, Marin DB, Peskind ER, Younki SG, Greenberg DA, Schnur E, Santoro J, Davis KL (1999) CSF β-amyloid, cognition, and ApoE genotype in Alzheimer’s disease. Neurology 52: 547–551PubMedGoogle Scholar
  67. Shoji M, Matsubara E, Kanai M, Watanabe M, Nakamura T, Tomidokoro Y, Shizuka M, Wakabayashi K, Igeta Y, Ikeda Y, Mizushima K, Amari M, Ishiguro K, Kawarabayashi T, Harigaya Y, Okamoto K, Hirai S (1998) Combination assay of CSF tau, Aβ(1–40) and Aβ(1–42)(43) as a biochemical marker of Alzheimer’s disease. J Neurol Sci 158: 134–140PubMedCrossRefGoogle Scholar
  68. Skoog I, Hesse C, Fredman P, Andreasson LA, Palmertz B, Blennow K (1997) Apolipoprotein E in cerebrospinal fluid in 85-year-old subjects. Arch Neurol 54: 267–272PubMedGoogle Scholar
  69. Skoog I, Wallin A, Fredman P, Hesse C, Aevarsson O, Karlsson I, Gottfries CG, Blennow K (1998) A population study on blood-brain barrier function in 85-year-olds: relation to Alzheimer’s disease and vascular dementia. Neurology 50: 966–971PubMedGoogle Scholar
  70. Small GW, Rosenthal M, Tourtellotte WW (1994) Central nervous system IgG synthesis rates in Alzheimer disease: possible differences in early-onset and late-onset subgroups. Alzheimer Dis Assoc Disord 8: 29–37PubMedCrossRefGoogle Scholar
  71. Statistica for Windows. Computer program manual (1995) StatSoft Inc, Tulsa, USAGoogle Scholar
  72. St George-Hyslop PH (2000) Molecular genetics of Alzheimer’s disease. Biol Psychiatry 47: 183–199PubMedCrossRefGoogle Scholar
  73. Sunderland T, Wolozin B, Galasko D, Levy J, Dukoff R, Bahro M, Lasser R, Motter R, Lehtimäki T, Seubert P (1999) Longitudinal stability of CSF tau in Alzheimer patients. Biol Psychiatry 46: 750–755PubMedCrossRefGoogle Scholar
  74. Tapiola T, Pirttilä T, Mikkonen M, Mehta PD, Alafuzoff I, Koivisto K, Soininen H (2000) Three-year-follow-up of cerebrospinal fluid tau, β-amyloid 42 and 40 concentrations in Alzheimer’s disease. Neurosci Lett 280: 119–122PubMedCrossRefGoogle Scholar
  75. Tato RE, Frank A, Hernanz A (1995) Tau protein concentrations in cerebrospinal fluid of patients with dementia of the Alzheimer type. J Neurol Neurosurg Psychiatry 59: 280–283PubMedCrossRefGoogle Scholar
  76. Valenti G (1996) Neuropeptide changes in dementia: pathogenic implications and diagnostic value. Gerontology 42: 241–256PubMedCrossRefGoogle Scholar
  77. Vandermeeren M, Mercken M, Vanmechelen E, Six J, van de Voorde A, Martin JJ, Cras P (1993) Detection of tau proteins in normal and Alzheimer’s disease cerebrospinal fluid with a sensitive enzyme-linked immunosorbent assay. J Neurochem 61: 1828–1834PubMedCrossRefGoogle Scholar
  78. Van Gool WA, Schenk DB, Bolhuis PA (1994) Concentrations of amyloid-β-protein in cerebrospinal fluid increase with age in patients free from neurodegenerative disease. Neurosci Lett 172: 122–124PubMedCrossRefGoogle Scholar
  79. Wisniewski T, Frangione B (1992) Apolipoprotein E: a pathological chaperone protein in patients with cerebral and systemic amyloid. Neurosci Lett 135: 235–238PubMedCrossRefGoogle Scholar
  80. Wisniewski T, Golabek A, Matsubara E, Ghiso J, Frangione B (1993) Apolipoprotein E: binding to soluble Alzheimer’s β-amvloid. Biochem Biophys Res Comm 192: 359–365PubMedCrossRefGoogle Scholar
  81. Wood JA, Wood PL, Ryan R, Graff-Radford NR, Pilapil C, Robitaille Y, Quirion R (1993) Cytokine indices in Alzheimer’s temporal cortex: no changes in mature IL- 1β or IL-1RA but increases in the associated acute phase proteins IL-6, α2-macroglobulin and C-reactive protein. Brain Res 629: 245–252PubMedCrossRefGoogle Scholar
  82. Yamada K, Kono K, Umegaki H, Yamada K, Iguchi A, Fukatsu T, Nakashima N, Nishiwaki H, Shimada Y, Sugita Y, Yamamoto T, Hasegawa T, Nabeshima T (1995) Decreased interleukin-6 level in the cerebrospinal fluid of patients with Alzheimer-type dementia. Neurosci Lett 186: 219–221PubMedCrossRefGoogle Scholar
  83. Yankner BA, Duffy LK, Kirschner DA (1990) Neurotrophic and neurotoxic effects of amyloid β protein: reversal by tachykinin neuropeptides. Science 250: 279–282PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2001

Authors and Affiliations

  • N. Rösler
    • 1
    • 2
  • I. Wichart
    • 1
  • K. A. Jellinger
    • 1
  1. 1.Ludwig Boltzmann Institute of Clinical NeurobiologyViennaAustria
  2. 2.Ludwig Boltzmann Institute of Clinical NeurobiologyPKH/B BuildingViennaAustria

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