Etiology Versus Pathogenesis: The Causes of Post-Translational Modifications of Host-Specified Brain Proteins to Amyloid Configuration

  • D. C. Gajdusek
Part of the Research and Perspectives in Alzheimer’s Disease book series (ALZHEIMER)


Since amyloid is deposited as neurofibrillary tangles, plaques, and vascular amyloid in brains of all the very aged (> 90 years), and this amyloid is biochemically the same as that in Alzheimer’s disease, Down’s syndrome, and Guamanian amyotrophic lateral sclerosis/Parkinsonism-dementia (ALS/PD), we know that no abnormal hereditable gene is necessary for such deposition. By isolating the gene for the precursor to this amyloid we are surely tracking pathogenesis of normal aging. Alzheimer’s disease, Down’s syndrome, and Guamanian ALS/PD. The same applies to isolating the gene for the normal host precursor protein for the much different amyloid of the scrapie-associated fibrils of unconventional viruses (scrapie-kuru-Creutzfeldt-Jakob disease) and the amyloid plaques of these diseases.


Neurofibrillary Tangle Amyloid Fibril Acta Pathol Cerebrovascular Amyloid Amyloid Enhance Factor 
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. Axelrad MA, Kisilevsky R (1980) Biological characterizations of amyloid enhancing factor. In: Glenner GG, Costa PP, de Freitas AF (eds) Amyloid and amyloidosis. Excerpta Medica, Amsterdam, pp 527–533Google Scholar
  2. Axelrad MA, Kisilevsky R, Willmer J, Chen SJ, Skinner M (1982) Further characterization of amyloid-enhancing factor. Lab Invest 47: 139–146PubMedGoogle Scholar
  3. Beyreuther K, Multhaup G, Simms G, Pottgiesser J, Schroeder W, Martins RN, Masters CL (1986) Neurofibrillary tangles of Alzheimer’s disease and "aged" Down’s syndrome contain the same protein as the amyloid of plaque cores and blood vessels. Disc Neurosci 3: 68–79Google Scholar
  4. Castaño EM, Frangione B (1988) Human amyloidosis, Alzheimer disease and related disorders. Lab Invest 58: 122–132PubMedGoogle Scholar
  5. Castaño EM, Ghiso J, Prelli F, Gorevic PD, Migheli A, Frangione B (1986) In vitro formation of amyloid fibrils from two synthetic peptides of different lengths homologous to Alzheimer’s disease beta protein. Biochem Biophys Res Commun 141: 782–789PubMedCrossRefGoogle Scholar
  6. Cohen AS (1965) The constitution and genesis of amyloid. Int Rev Exp Pathol 4: 159–243PubMedGoogle Scholar
  7. Glenner GG, Wong CW (1984 a) Alzheimer’s disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem Biophys Res Comm 120: 885–890PubMedCrossRefGoogle Scholar
  8. Glenner GG, Wong CW (1984b) Alzheimer’s disease and Down’s syndrome: sharing of a unique cerebrovascular amyloid fibril protein. Biochem Biophys Res Commun 122: 1131–1135PubMedCrossRefGoogle Scholar
  9. Gorevic PD, Castaño EM, Sarma R, Frangione B (1987) Ten to fourteen residue peptides of Alzheimer’s disease beta protein are sufficient for amyloid fibril formation and its characteristic X-ray diffraction pattern. Biochem Biophys Res Commun 147: 854–862PubMedCrossRefGoogle Scholar
  10. Guiroy DC, Miyazaki M, Multhaup G, Fischer P, Garruto RM, Beyreuther K, Masters CL, Simms G, Gibbs CJ, Jr, Gajdusek DC (1987) Amyloid of the neurofibrillary tangles of Guamanian parkinsonism-dementia and Alzheimer disease share identical amino acid sequence. Proc Natl Acad Sci USA 84: 2073–2077PubMedCrossRefGoogle Scholar
  11. Hardt F, Ranlov P (1968) Transfer amyloidosis. Acta Pathol Microbiol Scand 73: 549–558PubMedCrossRefGoogle Scholar
  12. Hol PR, van Andel ACJ, van Ederen AM, Draáyer J, Grays E (1985) Amyloid enhancing factor in hamster. Br J Exp Pathol 66: 689–697PubMedGoogle Scholar
  13. Hol PR, Snel FWJJ, Niewold ThA, Grays E (1986) Amyloid-enhancing factor (AEF) in the pathogenesis of AA-amyloidosis in the hamster. Virchows Arch (Cell Pathol) 52: 273–281CrossRefGoogle Scholar
  14. Janigan DT (1965) Experimental amyloidosis. Am J Pathol 47: 159–171PubMedGoogle Scholar
  15. Janigan DT, Druet RL (1968) Experimental murine amyloidosis in X-irradiated recipients of spleen homogenates or serum from sensitized donors. Am J Pathol 52: 381–390PubMedGoogle Scholar
  16. Janigan DT (1969) Pathogenetic mechanisms in protein-induced amyloidosis. Am J Pathol 55: 379–393PubMedGoogle Scholar
  17. Keizman I, Rimon A, Sohar E, Gafni J (1972) Amyloid accelerating factor. Acta Pathol Microbiol Scand [Suppl 233] 80:172–177Google Scholar
  18. Kirschner DA, Inouye H, Duffy LK, Sinclair A, Lind M, Selkoe DJ (1987) Synthetic peptide homologous to beta protein from Alzheimer disease forms amyloid-like fibrils in vitro. Proc Natl Acad Sci USA 84: 6953–6957PubMedCrossRefGoogle Scholar
  19. Kisilevsky R, Boudreau L (1983 a) Kinetics in amyloid deposition. I. The effects of amyloid-enhancing factor and splenectomy. Lab Invest 48: 53–59PubMedGoogle Scholar
  20. Kisilevsky R, Boudreau L, Foster D (1983 b) Kinetics of amyloid deposition. II. The effects of dimethylsulfoxide and colchicine therapy. Lab Invest 48: 60–67PubMedGoogle Scholar
  21. Masters CL, Simms G, Weinman NA, Multhaup G, McDonald BL, Beyreuther K (1985 a) Amyloid plaque core protein in Alzheimer disease and Down’s syndrome. Proc Natl Acad Sci USA 82: 4245–4249PubMedCrossRefGoogle Scholar
  22. Masters CL, Multhaup G, Simms G, Pottgiesser J, Martins RN, Beyreuther K (1985b) Neuronal origin of a cerebral amyloid: neurofibrillary tangles of Alzheimer’s disease contain the same protein as the amyloid of plaque cores and blood vessels. EMBO J 4: 2757–2763PubMedGoogle Scholar
  23. Niewold ThA, Hoi PR, van Andel ACJ, Lutz ETG, Grays E (1987) Enhancement of amyloid induction by amyloid fibril fragments in hamster. Lab Invest 56: 544–549PubMedGoogle Scholar
  24. Ranlov P (1967) The adoptive transfer of experimental mouse amyloidosis by intravenous injection of spleen cell extracts from casein-treated syngeneic donor mice. Acta Pathol Microbiol Scand 70: 321–335PubMedCrossRefGoogle Scholar
  25. Shirahama T, Lawless OJ, Cohen AS (1969) Heterologous transfer of amyloid - human to mouse. Proc Soc Exp Biol Med 130: 516–519PubMedGoogle Scholar
  26. Snow AD, Kisilevsky R (1985) Temporal relationship between glycosaminoglycan accumulation and amyloid deposition during experimental amyloidosis. Lab Invest 53: 37–44PubMedGoogle Scholar
  27. Teilum G (1964) Pathogenesis of amyloidosis. The two-phase cellular theory of local secretion. Acta Pathol Microbiol Scand 61: 21–45Google Scholar
  28. Varga J, Flinn MSM, Shirahama T, Rodgers OG, Cohen AS (1986) The induction of accelerated murine amyloid with human splenic extract. Virchows Arch (Cell Pathol) 51: 177–185CrossRefGoogle Scholar
  29. Werderlin O, Ranlov P (1966) Amyloidosis in mice produced by transplantation of spleen cells from casein-treated mice. Arch Pathol Microbiol Scand 68: 1–18Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1988

Authors and Affiliations

  • D. C. Gajdusek

There are no affiliations available

Personalised recommendations