Integrity of the blood-CSF barrier in dementia of Alzheimer type: CSF/serum ratios of albumin and IgG

  • L. Frölich
  • J. Kornhuber
  • R. Ihl
  • J. Fritze
  • K. Maurer
  • P. Riederer
Original Articles

Summary

Serum and cerebrospinal fluid (CSF) from 25 patients with dementia of Alzheimer type (DAT) and 25 controls were assayed for concentrations of albumin and IgG. The severity of dementia was rated with the Mini Mental State Examination. The CSF/serum ratio for albumin and IgG as well as the IgG index were used to evaluate blood-CSF barrier function in the respective groups. The control group was matched for age, sex and the indirect alcohol parameters, mean corpuscular volume and gamma-glutamyltranspeptidase. There were no signs of dysfunction of the blood-CSF barrier for proteins or signs of local synthesis of IgG in the central nervous system (CNS) of the demented patients. The permeability of the blood-CSF barrier appeared to be unrelated to dementia severity. The data do not support the hypothesis that a pathological leakage through the blood-CSF barrier facilitates the entry of extraneuronal proteins to the CNS, which might contribute to the pathophysiological process in DAT.

Key words

Albumin IgG Dementia of Alzheimer type Blood-CSF barrier Cerebrospinal fluid 

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References

  1. 1.
    Alafuzoff I, Adolfsson R, Bucht G, Winbald B (1983) Albumin and immunoglobulin in plasma and cerebrospinal fluid, and blood-cerebrospinal fluid barrier function in patients with dementia of Alzheimer type and multi-infarct dementia. J Neurol Sci 60:465–472CrossRefPubMedGoogle Scholar
  2. 2.
    Alafuzoff I, Adolfsson R, Grundke-Iqbal I, Winblad B (1987) Blood-brain barrier in Alzheimer dementia and non-demented elderly. Acta Neuropathol (Berl) 73:160–166CrossRefGoogle Scholar
  3. 3.
    Ben Menachem E, Persson L, Schechter PJ, Haegele KD, Huebert N, Hardenberg J (1989) Cerebrospinal fluid parameters in healthy volunteers during serial lumbar puncture. J Neurochem 52:632–635PubMedGoogle Scholar
  4. 4.
    Bohl J, Störkel S, Schulze E, Tschank G, Haas S, Krausbeck E, Gather W, Katzman K, Brocks D (1986) Alzheimer's disease: a cerebral amyloidosis. A cooperative study to correlate clinical, biochemical and pathoanatomical findings. Pharmacopsychiatry 19:196–197Google Scholar
  5. 5.
    Chapel HM, Esiri MM, Wilcock GK (1984) Immunoglobulin and other proteins in the cerebrospinal fluid of patients with Alzheimer's disease. J Clin Pathol 37:697–699PubMedGoogle Scholar
  6. 6.
    Cohen D, Eisdorfer C (1980) Serum immunoglobulins and cognitive status in the elderly. I. A population study. Br J Psychiatry 136:33–39PubMedGoogle Scholar
  7. 8.
    Elovaara I, Icén A, Palo J, Erkinjuntti T (1985) CSF in Alzheimer's Disease. Studies on blood-brain barrier function and intrathecal protein synthesis. J Neurol Sci 70:73–80CrossRefPubMedGoogle Scholar
  8. 9.
    Felgenhauer K (1982) Differentiation of the humoral immune response in inflammatory diseases of the central nervous system. J Neurol 228:223–237CrossRefPubMedGoogle Scholar
  9. 10.
    Folstein M, Folstein S, McHugh PR (1975) Mini-Mental state: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189–198CrossRefPubMedGoogle Scholar
  10. 11.
    Friedland RP, Budinger TF, Jagust WJ, Yano Y, Huesman RH, Knittel B (1985) Positron emission tomography and the blood-brain barrier in Alzheimer's disease. In: Cahn J, Lassen NA (eds) New brain imaging techniques in cerebrovascular diseases. Libbey Eurotext, London, pp 85–93Google Scholar
  11. 12.
    Frölich L, Eilles C, Ihl R, Maurer K, Lanczik M (1989) Stage-dependent reductions of regional cerebral blood flow measured by HMPAO-SPECT in dementia of Alzheimer type. Psychiatry Res 29:347–350CrossRefPubMedGoogle Scholar
  12. 13.
    Ganrot K, Laurell CB (1974) Measurement of IgG and albumin content of cerebrospinal fluid and its interpretation. Clin Chem 20:571–573PubMedGoogle Scholar
  13. 14.
    Glenner GG (1985) On causative theories in Alzheimer's disease. Hum Pathol 16:433–435PubMedGoogle Scholar
  14. 15.
    Glenner GG, Wong CW (1984) Alzheimer's disease and Down's syndrome: sharing of a unique cerebrovascular amyloid fibril protein. Biochem Biophys Res Commun 122:1131–1135CrossRefPubMedGoogle Scholar
  15. 16.
    Goldgaber D, Harris HW, Hla T, Maciag T, Donnelly RJ, Jacobsen JS, Vitek MP, Gajdusek DC (1989) Interleukin 1 regulates synthesis of amyloid beta-protein precursor mRNA in human endothelial cells. Proc Natl Acad Sci USA 86:7606–7610PubMedGoogle Scholar
  16. 17.
    Griffin WST, Stanley LC, Ling C, White L, MacLeod V, Perrot LJ, White III CL, Araoz C (1989) Brain interleukin 1 and S-100 immunoreactivity are elevated in Down's syndrome and Alzheimer disease. Proc Natl Acad Sci USA 86:7611–7615PubMedGoogle Scholar
  17. 18.
    Henderson AS, Henderson JH (1988) Etiology of dementia of Alzheimer's type. Dahlem Konferenzen. Wiley, ChichesterGoogle Scholar
  18. 19.
    Joachim CL, Mori H, Selkoe DJ (1989) Amyloid beta-protein deposition in tissues other than brain in Alzheimer's disease. Nature 341:226–230CrossRefPubMedGoogle Scholar
  19. 20.
    Jonker C, Eikelenboom P, Tavenier P (1982) Immunological indices in the cerebrospinal fluid of patients with presenile dementia of the Alzheimer type. Br J Psychiatry 140:44–49PubMedGoogle Scholar
  20. 21.
    Kang J, Lemaire HG, Unterbeck A, Salbaum M, Masters CL, Grzeschik KH, Multhaup G, Beyreuther K, Müller-Hill B (1987) The precursor of Alzheimer's disease A4 protein resembles a cell-surface receptor. Nature 325:733–736CrossRefGoogle Scholar
  21. 22.
    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 8:21–25CrossRefPubMedGoogle Scholar
  22. 23.
    Kornhuber J, Kaiserauer CH, Kornhuber AW, Kornhuber ME (1987) Alcohol consumption and blood-cerebrospinal fluid barrier dysfunction in man. Neurosci Lett 79:218–222CrossRefPubMedGoogle Scholar
  23. 24.
    Leonardi A, Gandolfo C, Arata L, Vecchia R (1985) The integrity of the blood-brain barrier in Alzheimer's type and multiinfarct dementia by the study of albumin and IgG in serum and cerebrospinal fluid. J Neurol Sci 67:253–261CrossRefPubMedGoogle Scholar
  24. 25.
    Mandlybur TI (1975) The incidence of cerebral amyloid angiopathy in Alzheimer's disease. Neurology 25:120–126PubMedGoogle Scholar
  25. 26.
    Mann DMA, Jones D, Prinja D, Purkiss MS (1990) The prevalence of amyloid (A4) protein deposits within the cerebral and cerebellar cortex in Down's syndrome and Alzheimer's disease. Acta Neuropathol (Berl) 80:318–327CrossRefGoogle Scholar
  26. 27.
    Maurer K, Dierks T (1987) Topographic brain mapping of EEG and evoked potentials in psychiatry and neurology. Z EEG EMG 18:4–12Google Scholar
  27. 28.
    Maurer K, Ihl R, Dierks T (1988) Topographie der P300 in der Psychiatrie. II. Kognitive P300 Felder bei Demenz. Z EEG EMG 19:26–29Google Scholar
  28. 29.
    McKhann G, Drachman D, Folstein M, Katzman R, Price DL, Stadlan M (1984) Clinical diagnosis of Alzheimer's disease. A report of the NINCDS/ADRDA work group under the auspices of the Department of Health and Human Services task force on Alzheimer's disease. Neurology 34:939–944PubMedGoogle Scholar
  29. 30.
    Molsä PK, Paljärvi L, Rinne JO, Rinne UK, Säkö E (1985) Validity of the clinical diagnosis in dementia: a prospective clinicopathological study. J Neurol Neurosurg Psychiatry 48: 1085–1090PubMedGoogle Scholar
  30. 31.
    Pardridge WM, Vinters HV, Miller BL, Tourtellotte WW, Eisenberg JB, Yang J (1987) High molecular weight Alzheimer's disease amyloid peptide immunoreactivity in human serum and CSF is an immunoglobulin G. Biochem Biophys Res Commun 145:241–248CrossRefPubMedGoogle Scholar
  31. 32.
    Reiber H (1990) The discrimination between blood-CSF barrier dysfunction and inflammatory reaction of the CNS by a recent evaluation graph for the protein profile of the cerebrospinal fluid. J Neurol 224:89–99CrossRefGoogle Scholar
  32. 33.
    Rosen WG, Terry RD, Fuld PA, Katzman R, Peck A (1980) Pathologic verification of ischemic score in differentiation of dementias. Ann Neurol 7:486–488CrossRefPubMedGoogle Scholar
  33. 34.
    Schlageter NL, Carson RE, Rapoport SI (1987) Examination of blood-brain barrier permeability in dementia of the Alzheimer type with [68Ga]EDTA and positron emission tomography. J Cereb Blood Flow Metab 7:1–8PubMedGoogle Scholar
  34. 35.
    Tanzi RE, Gusella JF, Watkins PC, Bruns GAP, StGeorge-Hyslop P, Keuren M van, Patterson D, Pagan S, Kurnit DM, Neve RL (1987) Amyloid beta protein gene: cDNA, mRNA distribution and genetic linkage near the Alzheimer locus. Science 235:880–884PubMedGoogle Scholar
  35. 36.
    Tibbling G, Link H, Ohman S (1977) Principles of albumin and IgG analyses in neurological disorders. 1. Establishment of reference values. Scand J Clin Lab Invest 37:385–390PubMedGoogle Scholar
  36. 37.
    Tomlinson BE, Blessed G, Roth M (1970) Observations on the brains of demented old people. J Neurol Sci 11:205–242CrossRefPubMedGoogle Scholar
  37. 38.
    Vinters HV, Pardridge WM (1986) The blood brain barrier in Alzheimer's disease. Can J Neurol Sci 13:446–448PubMedGoogle Scholar
  38. 39.
    Wade JPH, Mirsen TR, Hachinski VC, Fisman M, Lau C, Merskey H (1987) The clinical diagnosis of Alzheimer's disease. Arch Neurol 44:24–29PubMedGoogle Scholar
  39. 40.
    Wisniewski HM, Kozlowski PB (1982) Evidence for blood-brain barrier changes in senile dementia of the Alzheimer type (SDAT). In: Sinex FM, Merril CR (eds) Alzheimer's disease, Down's syndrome and aging. Ann NY Acad Sci 396:119–129Google Scholar

Copyright information

© Springer-Verlag 1991

Authors and Affiliations

  • L. Frölich
    • 1
  • J. Kornhuber
    • 1
  • R. Ihl
    • 1
  • J. Fritze
    • 1
  • K. Maurer
    • 1
  • P. Riederer
    • 1
  1. 1.Department of PsychiatryUniversity of WürzburgWürzburgFederal Republic of Germany

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