Skip to main content

Advertisement

Log in

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

  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

Summary

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.

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

  • 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: 673–680

    Article  PubMed  CAS  Google Scholar 

  • 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: 5–8

    Article  PubMed  CAS  Google Scholar 

  • 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: 2–10

    PubMed  CAS  Google Scholar 

  • Bancher C, Jellinger K, Wichart I (1998) Biological markers for the diagnosis of Alzheimer’s disease. J Neural Transm [Suppl] 53: 185–197

    CAS  Google Scholar 

  • 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: 111–114

    Article  PubMed  CAS  Google Scholar 

  • Blacker D, Tanzi RE (1998) The genetics of Alzheimer’s disease – current status and future prospects. Arch Neurol 55: 294–296

    Article  PubMed  CAS  Google Scholar 

  • 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: 223–235

    CAS  Google Scholar 

  • 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: 79–86

    PubMed  CAS  Google Scholar 

  • Blennow K, Hesse C, Fredman P (1994) Cerebrospinal fluid apolipoprotein E is reduced in Alzheimer’s disease. Neuroreport 5: 2534–2536

    Article  PubMed  CAS  Google Scholar 

  • 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: 17–20

    Article  PubMed  CAS  Google Scholar 

  • 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: 10061–10065

    Article  PubMed  CAS  Google Scholar 

  • 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: 167–176

    Article  PubMed  CAS  Google Scholar 

  • Consensus Report of the Working Group on: “Molecular and Biochemical Markers of Alzheimer’s Disease” (1998) Neurobiol Aging 19: 109–116

    Article  Google Scholar 

  • 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: 928–934

    Article  PubMed  CAS  Google Scholar 

  • 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: 346–351

    Article  PubMed  CAS  Google Scholar 

  • Dickson DW (1997) The pathogenesis of senile plaques. J Neuropathol Exp Neurol 56: 321–329

    Article  PubMed  CAS  Google Scholar 

  • 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: 523–530

    Article  PubMed  CAS  Google Scholar 

  • Fishman RA (1992) Cerebrospinal fluid in diseases of the nervous system, 2nd edn. Saunders, Philadelphia, p 339

    Google Scholar 

  • 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: 189–198

    Article  PubMed  CAS  Google Scholar 

  • 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: 689–694

    Article  PubMed  CAS  Google Scholar 

  • 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: 363–366

    Article  PubMed  Google Scholar 

  • 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: 161–169

    Article  PubMed  CAS  Google Scholar 

  • Gahtan E, Overmier JB (1999) Inflammatory pathogenesis in Alzheimer’s disease: biological mechanisms and cognitive sequeli. Neurosci Biobehav Rev 23: 615–633

    Article  PubMed  CAS  Google Scholar 

  • Galasko D (1998) Cerebrospinal fluid levels of Aβ42 and tau: potential markers of Alzheimer’s disease. J Neural Transm [Suppl] 53: 209–221

    CAS  Google Scholar 

  • 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: 937–945

    Article  PubMed  CAS  Google Scholar 

  • 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: 101–108

    Article  PubMed  CAS  Google Scholar 

  • Goedert M (1993) Tau protein and the neurofibrillary pathology of Alzheimer’s disease. Trends Neurosci 16: 460–465

    Article  PubMed  CAS  Google Scholar 

  • 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: 133–135

    Article  PubMed  CAS  Google Scholar 

  • 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: 145–159

    CAS  Google Scholar 

  • 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: 99–102

    Article  PubMed  CAS  Google Scholar 

  • 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: 445–452

    Article  PubMed  CAS  Google Scholar 

  • 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: 143–146

    Article  PubMed  CAS  Google Scholar 

  • 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: 9–19

    Article  PubMed  CAS  Google Scholar 

  • 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: 511–517

    Article  PubMed  CAS  Google Scholar 

  • 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: 414–415

    Google Scholar 

  • 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: 544–551

    Article  Google Scholar 

  • 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: 1555–1562

    PubMed  CAS  Google Scholar 

  • 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: 91–94

    Article  PubMed  CAS  Google Scholar 

  • Jellinger KA (1998) The neuropathological diagnosis of Alzheimer disease. J Neural Transm [Suppl] 53: 97–118

    CAS  Google Scholar 

  • Jellinger KA (1999) What is new in degenerative dementia disorders? Wien Klin Wochenschr 111: 682–704

    PubMed  CAS  Google Scholar 

  • 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: 1498–1504

    PubMed  CAS  Google Scholar 

  • 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: 17–26

    Article  PubMed  CAS  Google Scholar 

  • 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: 21–25

    Article  PubMed  CAS  Google Scholar 

  • 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: 7247–7251

    Article  PubMed  CAS  Google Scholar 

  • 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: 215–227

    Article  PubMed  CAS  Google Scholar 

  • 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: 91–94

    Article  PubMed  CAS  Google Scholar 

  • 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: 253–261

    Article  PubMed  CAS  Google Scholar 

  • 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: 85–88

    Article  Google Scholar 

  • Malek-Ahmadi P (1992) Substance P and neuropsychiatry disorders: an overview. Neurosci Biobehav Rev 16: 365–369

    Article  PubMed  CAS  Google Scholar 

  • 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: 235–240

    Article  PubMed  CAS  Google Scholar 

  • 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: 29–32

    Article  PubMed  Google Scholar 

  • 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: 506–511

    Article  PubMed  CAS  Google Scholar 

  • McGeer PL, Rogers J, McGeer EG (1994) Neuroimmune mechanisms in Alzheimer disease pathogenesis. Alzheimer Dis Assoc Disord 8: 149–158

    Article  PubMed  CAS  Google Scholar 

  • 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: 939–944

    PubMed  CAS  Google Scholar 

  • 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: 210–213

    Article  PubMed  CAS  Google Scholar 

  • 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: 33–39

    Article  PubMed  CAS  Google Scholar 

  • 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: 643–648

    Article  PubMed  CAS  Google Scholar 

  • 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: 219–226

    Article  PubMed  CAS  Google Scholar 

  • 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: 163–166

    Article  PubMed  CAS  Google Scholar 

  • 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: 921

    Article  Google Scholar 

  • 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: 189–193

    PubMed  Google Scholar 

  • Pokier J (1994) Apolipoprotein E in animal models of CNS injury and in Alzheimer’s disease. Trends Neurosci 17: 525–530

    Article  Google Scholar 

  • 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: 319–328

    Article  PubMed  CAS  Google Scholar 

  • 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: 452–454

    Article  Google Scholar 

  • 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: 237–238

    Google Scholar 

  • 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: 547–551

    PubMed  CAS  Google Scholar 

  • 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: 134–140

    Article  PubMed  CAS  Google Scholar 

  • 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: 267–272

    PubMed  CAS  Google Scholar 

  • 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: 966–971

    PubMed  CAS  Google Scholar 

  • 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: 29–37

    Article  PubMed  CAS  Google Scholar 

  • Statistica for Windows. Computer program manual (1995) StatSoft Inc, Tulsa, USA

  • St George-Hyslop PH (2000) Molecular genetics of Alzheimer’s disease. Biol Psychiatry 47: 183–199

    Article  PubMed  CAS  Google Scholar 

  • 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: 750–755

    Article  PubMed  CAS  Google Scholar 

  • 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: 119–122

    Article  PubMed  CAS  Google Scholar 

  • 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: 280–283

    Article  PubMed  CAS  Google Scholar 

  • Valenti G (1996) Neuropeptide changes in dementia: pathogenic implications and diagnostic value. Gerontology 42: 241–256

    Article  PubMed  CAS  Google Scholar 

  • 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: 1828–1834

    Article  PubMed  CAS  Google Scholar 

  • 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: 122–124

    Article  PubMed  Google Scholar 

  • Wisniewski T, Frangione B (1992) Apolipoprotein E: a pathological chaperone protein in patients with cerebral and systemic amyloid. Neurosci Lett 135: 235–238

    Article  PubMed  CAS  Google Scholar 

  • 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: 359–365

    Article  PubMed  CAS  Google Scholar 

  • 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: 245–252

    Article  PubMed  CAS  Google Scholar 

  • 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: 219–221

    Article  PubMed  CAS  Google Scholar 

  • Yankner BA, Duffy LK, Kirschner DA (1990) Neurotrophic and neurotoxic effects of amyloid β protein: reversal by tachykinin neuropeptides. Science 250: 279–282

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rösler, N., Wichart, I. & Jellinger, K.A. Clinical significance of neurobiochemical profiles in the lumbar cerebrospinal fluid of Alzheimer’s disease patients. J Neural Transm 108, 231–246 (2001). https://doi.org/10.1007/s007020170091

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s007020170091

Keywords

Navigation