Acta Neuropathologica

, Volume 73, Issue 3, pp 240–246 | Cite as

Alzheimer dementia and Pick's disease: neurofibrillary tangles and Pick bodies are associated with identical phosphorylated neurofilament epitopes

  • J. Ulrich
  • M. Haugh
  • B. H. Anderton
  • A. Probst
  • C. Lautenschlager
  • B. His
Regular Papers


Section of formaldehyde-fixed paraffinembedded cortical and hippocampal brain tissue from five cases with senile dementia of Alzheimer type (SDAT) and five cases with Pick's disease (PD) were immunostained with the monoclonal antibodies (mabs) 147, RT 97, BF 10 and 8D8 with and without pretreatment with alkaline phosphatase (AP) or trypsin (Tr). The mabs 147, RT 97 and BF 10 had previously been demonstrated to bind exclusively to phosphorylated epitopes of neurofilament proteins, while mab 8D8 is shown in this report to bind mainly, but not exclusively, to phosphorylated neurofilament epitopes. The mabs RT 97, BF 10 and 8D8, but not 147 stain most, if not all, Pick bodies (PB) and Alzheimer neurofibrillary tangles (NFT). When sections are pretreated with AP or Tr the immunostaining with mab BF 10 is very resistent in both PB and NFT. This resistance of PB and NFT is in contrast to the reduced staining of axons and of swollen cells in PD by the same enzymatic pretreatment. Immunostaining with mab RT 97 of PB and NFT is reduced moderately by AP and considerably by Tr. Only when stained with mab 8D8 is there a discrepancy between PB and NFT in their reaction to the pretreatment with AP: NFT staining with mab 8D8 is not affected, while that of PB is abolished. Thus, in spite of their different ultrastructure, PB and NFT are very similar immunocytochemically and in the accessibility of their phosphorylated epitopes to enzymatic treatment.

Key words

Senile dementia of Alzheimer type Pick's disease Monoclonal antibodies Pick bodies Alzheimer neurofibrillary tangles 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Alzheimer A (1907) Über eine eigenartige Erkrankung der Hirnrinde. Zentralbl Gesamte Neurol Psychiatr 18:177–179Google Scholar
  2. Anderton BH, Thorpe R, Cohen J, Selvendran S, Woodhams P (1980) Specific neuronal localisation by immunofluorescence of 10 nm filament polypeptides. J Neurocytol 9:835–844Google Scholar
  3. Anderton BH, Breinburg D, Downes MJ, Green PhJ, Tomlinson BE, Ulrich J (1982) Monoclonal antibodies show that neurofibrillary tangles share antigenic determinants with normal neurofilaments. Nature 298:84–86Google Scholar
  4. Anderton BH, Haugh MC, Kahn J, Miller C, Probst A, Ulrich J (1985) The nature of neurofibrillary tangles. In: Traber J, Gispen WH (eds) Senile dementia of the Alzheimer type. Springer, Berlin Heidelberg New York, pp 205–216Google Scholar
  5. Blocq P, Marinesco G (1892) Sur les lésions et la pathogénie de l'épilepsie dite essentielle. Sem Med 12:445–446Google Scholar
  6. Brion S, Mikol J, Primares A (1973) Recent findings in Pick's disease. Prog Neuropathol 2:421–451Google Scholar
  7. Brion JP, Couck AM, Flament-Durand J (1985) Neurofibrillary tangles of Alzheimer's disease: an immunohistochemical study. J Submicrosc Cytol 17:89–96Google Scholar
  8. Glenner GG, Wong CM (1984a) Alzheimer's disease: initial report of the purification and characterisation of a novel cerebrovascular amyloid protein. Biochem Biophys Res Commun 120:885–890Google Scholar
  9. Glenner GG, Wong CM (1984b) Alzheimer's disease and Down's syndrome: sharing of a unique cerebrovascular amyloid fibril protein. Biochem Biophys Res Commun 122:1131–1132Google Scholar
  10. Haugh MC, Probst A, Ulrich J, Kahn J, Anderton BH (1986) Alzheimer neurofibrillary tangles contain phosphorylated and hidden neurofilament epitopes. J Neurol Neurosurg Psychiatry 49:1213–1220Google Scholar
  11. Hirano A, Zimmerman HM (1962) Alzheimer neurofibrillary changes. A topographic study. Arch Neurol 7:227–242Google Scholar
  12. Hsu SM, Raine L, Fanger H (1981) Use of avidin-biotin complex (ABC) in immunoperoxydase techniques. J Histochem Cytochem 29:577–580Google Scholar
  13. Jamada M, Mehrain P (1968) Verteilungsmuster der senilen Veränderungen im Gehirn. Die Beteiligung des limbischen Systems bei hirnatrophischen Prozessen des Seniums und bei Morbus Alzheimer. Arch Psychiatr Z Ges Neurol 211: 308–324Google Scholar
  14. Kahn J, Green PG, Thorpe R, Anderton BH (1980) Immunohistochemistry of neurofilaments in Alzheimer's disease. J Clin Exp Gerontol 2:199–210Google Scholar
  15. Kidd M (1963) Paired helical filaments in electron microscopy of Alzheimer's disease. Nature 197:192–193Google Scholar
  16. Kosik KS, Joachim CL, Selkoe DJ (1986) Microtubule-associated protein, tau, is a major antigenic determinant of paired helical filaments in Alzheimer's disease. Proc Natl Acad Sci USA 83:4044–4048Google Scholar
  17. Masters CL, Multhaup G, Simms G, Pottgiesser J, Martins RN, Beyreuther K (1985) 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 4:2757–2763Google Scholar
  18. Mikol J, Brion S, Guicharnod L, Waks O (1980) A new case of Pick's disease. Anatomical and ultrastructural studies. Acta Neuropathol (Berl) 49:57–61Google Scholar
  19. Miller CJ, Brion JP, Calvert R, Chin TK, Eagles PAM, Downes MJ, Flament-Durand J, Haugh M, Probst A, Ulrich J, Anderton BH (1986a) Alzheimer's paired helical filaments share epitopes with neurofilament side arms. EMBO J 5:269–276Google Scholar
  20. Miller C, Haugh M, Kahn J, Anderton BH (1986b) The cytoskeleton and neurofibrillary tangles in Alzheimer's disease. Trends Neuro Sci 9:76–81Google Scholar
  21. Pick A (1906) Über einen weiteren Symptomenkomplex im Rahmen der dementia senilis, bedingt durch umschriebene stärkere Hirnatrophie (gemischte Apraxie). Monatsschr Psychiatr Neurol 19:97–108Google Scholar
  22. Probst A, Anderton BH, Ulrich J, Kohler R, Kahn J, Heitz Ph U (1983) Pick's disease: an immunocytochemical study of neuronal changes. Acta Neuropathol (Berl) 60:175–182Google Scholar
  23. Rasool CG, Selkoe DJ (1985) Sharing of specific antigens by degenerating neurons in Pick's disease and Alzheimer's disease. N Engl J Med 312:700–705Google Scholar
  24. Schochet SS, Lampert PW, Lindenberg R (1968) Fine structure of Pick and Hirano bodies in a case of Pick's disease. Acta Neuropathol (Berl) 11:330–337Google Scholar
  25. Schwartz P (1970) Amyloidosis: cause and manifestations of senile deterioration. Thomas, SpringfieldGoogle Scholar
  26. Selkoe DJ, Abraham CR, Poddling MB, Duffy LK (1986) Isolation of low molecular weight proteins from amyloid plaque fibers in Alzheimer's disease. J Neurochem 46:1820–1834Google Scholar
  27. Sternberger LA (1986) Immunocytochemistry 3rd ed. Wiley, New York pp 103 ffGoogle Scholar
  28. Sternberger LA, Sternberger NH (1983) Monoclonal antibodies distinguish phosphorylated and non-phosphorylated forms of neurofilaments in situ. Proc Natl Acad Sci USA 80: 6126–6130Google Scholar
  29. Sternberger NH, Sternberger LA, Ulrich J (1985) Aberrant neurofilament phosphorylation in Alzheimer's disease. Proc Natl Acad Sci USA 82:4274–4276Google Scholar
  30. Takauchi S, Hosomi M, Marasigan S, Sato M, Hayashi S, Miyoshio K (1984) An ultrastructural study of Pick bodies. Acta Neuropathol (Berl) 64:344–348Google Scholar
  31. Wischik CM, Crowther RA (1986) Subunit structure of the Alzheimer tangle. Br Med Bull 42:51–56Google Scholar
  32. Wong CM, Quaranta V, Glenner GG (1985) Neuritic plaques and cerebrovascular amyloid in Alzheimer's disease are antigenically related. Proc Natl Acad Sci USA 82:8729–8732Google Scholar

Copyright information

© Springer-Verlag 1987

Authors and Affiliations

  • J. Ulrich
    • 1
  • M. Haugh
    • 2
  • B. H. Anderton
    • 2
  • A. Probst
    • 1
  • C. Lautenschlager
    • 1
  • B. His
    • 1
  1. 1.Neuropathology Division, Department of PathologyUniversity of BaselBaselSwitzerland
  2. 2.Department of ImmunologySt. George's Hospital Medical SchoolLondonUK

Personalised recommendations