Immunodiagnosis and Immunotherapy of Patients with Alzheimer’s Syndrome

  • H. H. Fudenberg
  • V. K. Singh
Part of the Research and Perspectives in Alzheimer’s Disease book series (ALZHEIMER)


We and others have shown unique structural and functional similarities of central nervous system (CNS) cells and peripheral blood immune cells. Hence, studies of various immune cells in peripheral blood make possible longitudinal studies of patients with CNS disorders, especially of the effects of therapy, without requiring serial brain biopsies. Using this approach in Alzheimer’s disease (AD), we found aberrations of both cellular immunity and humoral immunity.

Depending upon the nature of the immune deficits and patients’ responsiveness to appropriate immunomodulant therapy, we have thus far distinguished four subsets of AD patients: one subset with defect (membrane fluidity) of a specific T cell and who respond to pyrrolidone therapy; a second subset with serum antibodies to neuron-axon filament proteins — these patients improve clinically after therapy with dialyzable leucocyte extract (DLE); a third subset with antibodies to brain antigens (autoimmune) for whom therapy has not yet been developed; and a fourth subset with none of the abnormalities mentioned above, probably heterogeneous due to multiple biochemical deficiencies. We believe that different therapeutic modalities will be necessary for different subsets, much like the situation with other “diseases” such as anemia and diabetes. These results provide additional evidence that AD is a syndrome, not a single disease. Additionally, the clinical improvement demonstrated that the defective function in AD is not due to the relevant neuronal cells being dead, but because they are either atrophied or their function is suppressed.


Congenital Adrenal Hyperplasia Chronic Granulomatous Disease Dialyzable Leucocyte Extract Brain Antigen Peripheral Blood Immune Cell 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Ammann AJ, Fudenberg HH (1976) Immunodeficiency diseases. In: Fudenberg HH, Stites DP, Caldwell JL, Wells JV (eds) Basic and clinical immunology. Lange Medical, Los Altos, CA, pp 391–421Google Scholar
  2. Arnason BG (1985) Multiple sclerosis, allied central nervous system diseases, and immune-mediated neuropathies. In: Rose NR, Mackay IR (eds) The autoimmune diseases. Academic, New York, pp 399–427Google Scholar
  3. Bandle EF, Wendt G, Ranalder UB, Trautmann KH (1984) 2-Pyrrolidinone and succinimide endogenously present in several mammalian species. Life Sci 35: 2205–2212Google Scholar
  4. Beck OE (1981) Distribution of virus antibody activity among human IgG subclasses. Clin Exp Immunol 43: 626–632PubMedGoogle Scholar
  5. Burgio GR, Ugazio A, Nespoli L, Maccario R (1983) Down’s syndrome: a model of immunodeficiency. Birth Defects 19: 325–327PubMedGoogle Scholar
  6. Chou YK, Stanley W, Virella G, Kilpatrick JM, Fudenberg HH (1987) Generation of phenotypically distinct macrophage-hepatoma hybrid clones. Immunobiology, in pressGoogle Scholar
  7. Dabrowski MP, Bernstein BK, Stasiak A, Gajkowski K, Korniluk S (1987) Immunologic and clinical evaluation of multiple sclerosis patients treated with corticosteroids and/or calf thymic hormones. Ann NY Acad Sci 496: 697–706PubMedCrossRefGoogle Scholar
  8. Dawkins RL, Garlepp MJ (1985) Autoimmune diseases of muscle: myasthenia gravis and myositis. In: Rose NR, Mackay IR (eds) The autoimmune diseases. Academic, New York, pp 591–615Google Scholar
  9. Dirienzo W, Stefanini GF, Singh VK, Paulling EE, Canonica GW, Fudenberg HH (1986) Does normal lymphocyte DNA synthesis in response to PHA exclude cell-mediated immunodepression? Clin Immunol Immunopathol 41: 227–235PubMedCrossRefGoogle Scholar
  10. Fillit H, Luine VN, Reisberg B, Amador R, McEwen B, Zabriskie JB (1985) Studies of the specificity of antibrain antibodies in Alzheimer’s disease. Neurol Neurobiol 18: 307–318Google Scholar
  11. Fontana A, Fierz W, Wekerle H (1984) Astrocytes present myelin basic protein to encephalitogenic T-cell lines. Nature 307: 273–276PubMedCrossRefGoogle Scholar
  12. Fudenberg HH, Whitten HD, Arnaud P, Khansari N (1984a) Is Alzheimer’s disease an immunological disorder? Observations and speculations. Clin Immunol Immunopathol 32: 127–131PubMedCrossRefGoogle Scholar
  13. Fudenberg HH, Whitten HD, Arnaud P, Khansari N, Tsang KY, Harnes CG (1984b) Immune diagnosis of a subset of Alzheimer’s disease with preliminary implications for immunotherapy. Biomed Pharmacother 38: 290–297PubMedGoogle Scholar
  14. Galbraith GMP, Emerson D, Fudenberg HH, Gibbs CJ, Gajdusek DC (1986) Antibodies to neurofilament protein in retinitis pigmentosa. J Clin Invest 78: 865–869PubMedCrossRefGoogle Scholar
  15. Glenner GG (1985) On causative theories in Alzheimer’s disease. Hum Pathol 16: 433–435PubMedCrossRefGoogle Scholar
  16. Hammarstrom L, Smith CIE (1986) Immunoglobulin isotype diversity and its functional significance. In: French MAH (ed) Immunoglobulins in health and disease. MTP, London, pp 31–53CrossRefGoogle Scholar
  17. Mann DMA (1985) The neuropathology of Alzheimer’s disease: a review with pathogenic, etiological and therapeutic considerations. Mech Ageing Dev 31: 213–255PubMedCrossRefGoogle Scholar
  18. Rodgaard A, Nielsen FC, Djurup R, Somnier F, Gammeltoft S (1987) Acetylcholine receptor antibody in myasthenia gravis: predominance of IgG subclasses 1 and 3. Clin Exp Immunol 67:82–88PubMedGoogle Scholar
  19. Siber G, Schur PH, Aisenberg AC, Weitzman SA, Schiffman G (1980) Correlation between serum IgG-2 concentrations and the antibody response to bacterial polysaccharide antigens. N Engl J Med 303: 178–182PubMedCrossRefGoogle Scholar
  20. Singh VK, Fudenberg HH (1986 a) Can blood immunocytes be used to study neuropsychiatrie disorders? J Clin Psychiatry 47: 592–595Google Scholar
  21. Singh VK, Fudenberg HH (1986b) Detection of brain autoantibodies in the serum of patients with Alzheimer’s disease but not Down’s syndrome. Immunol Lett 12: 277–280PubMedCrossRefGoogle Scholar
  22. Singh VK, Fudenberg HH (1986c) Immunologic approach to etiology and therapy of neuropsychiatric disorders. In: Bignami A, Bolis L, Gadjusek DC (eds) Molecular mechanisms for pathogenesis of central nervous system disorders, F.E. S.N. Discussion in Neurosciences, vol 3, pp 120–124Google Scholar
  23. Singh VK, Fudenberg HH (1986 d) Immunopharmacological approach to the study of chronic brain disorders. Prog Drug Res 30: 345–363PubMedGoogle Scholar
  24. Singh VK, Fudenberg HH (1987) Increase of immunoglobulin G3 subclass is related to brain autoantibody in Alzheimer’s disease but not in Down’s syndrome. J Clin Immunol, in pressGoogle Scholar
  25. Singh VK, Fudenberg HH, Brown FR III (1987) Immunologic dysfunction: simultaneous study of Alzheimer’s and older Down’s patients. Mech Ageing Dev 37: 257–264CrossRefGoogle Scholar
  26. Tanzi RE, St. George-Hyslop PH, Haines JL, Polinsky RJ, Nee L, Foncin JF, Neve RL, McClatchey AI, Conneally PM, Gusella JF (1987) The genetic defect in familial Alzheimer’s disease is not tightly linked to the amyloid beta-protein gene. Nature 329: 156–157PubMedCrossRefGoogle Scholar
  27. Toh BH, Gibbs CJ, Gajdusek DC, Goudsmit J, Dahl D (1985) The 200- and 150-kDa neurofilament proteins react with IgG autoantibodies from patients with kuru, Creutzfeldt-Jacob disease, and other neurological diseases. Proc Natl Acad Sci USA 82: 3485–3489Google Scholar
  28. Van Broeckhoven C, Genthe AM, Vandenberghe A, Horsthemke B, Backhovens H, Raeymaekers P, Van Hul W, Wehnert A, Gheuens J, Cras P, Bruyland M, Martin JJ, Salbaum M, Multhaup G, Masters CL, Beyreuther K, Gurling HMD, Mullan MJ, Holland A, Barton A, Irving N, Williamson R, Richards SJ, Hardy JA (1987) Failure of familial Alzheimer’s disease to segregate with the A4-amyloid gene in several European families. Nature 329: 153–155PubMedCrossRefGoogle Scholar
  29. Vissinga CS, Dirven CJAM, Dirven FA, Steinmeyer VA, Benner R, Boersma WJA (1987) Deterioration of cellular immunity during aging. The relationship between age-dependent impairment of delayed-type hypersensitivity reactivity, interleukin-2 production capacity, and frequency of Thy1+, Lyt-2 cells in C57BL/Ka and CBA/Rij mice. Cell Immunol 108: 323–334PubMedCrossRefGoogle Scholar
  30. Walford RL, Gossett TC, Naeim F, Tarn CF, Van Lancker JL, Bennett EV, Chia D, Sparkes RS, Fahey JL, Spina C, Gatti RA, Medici MA, Grossman H, Hibrawi H, Motola M (1981) Immunological and biochemical studies of Down’s syndrome as a model of accelerated aging. In: Segre D, Smith L (eds) Immunological aspects of aging. Dekker, New York, pp 479–532Google Scholar
  31. Weetman AP, Cohen S (1986) The IgG subclass distribution of thyroid autoantibodies. Immunol Lett 13: 335–341PubMedCrossRefGoogle Scholar
  32. Weksler ME (1980) The immune system and the aging process in man. Proc Soc Exp Biol Med 165: 200–203PubMedGoogle Scholar
  33. White PC, New MI, Dupont B (1987) Congenital adrenal hyperplasia. N Engl J Med 316:1519–1524PubMedCrossRefGoogle Scholar
  34. Wisniewski HM, Merz GS, Carp RI (1985) Current hypothesis of the etiology and pathogenesis of senile dementia of the Alzheimer’s type. Interdise Top Gerontol 19: 45–53Google Scholar
  35. Zubenko GS, Cohen BM, Reynolds CF, Boller F, Malinakova I, Keefe N (1987) Platelet membrane fluidity in Alzheimer’s disease and major depression. Am J Psychiatry 144: 860–868PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1988

Authors and Affiliations

  • H. H. Fudenberg
  • V. K. Singh

There are no affiliations available

Personalised recommendations