Acta Neuropathologica

, Volume 71, Issue 1–2, pp 154–158 | Cite as

Phosphorylation of neurofilaments is altered in aluminium intoxication

  • A. Bizzi
  • P. Gambetti
Original Works


A series of monoclonal antibodies that distinguish phosphorylated and nonphosphorylated neurofilament (NF) epitopes was used to immunostain brain stem neurons from control rabbits and from rabbits chronically intoxicated with Aluminium (Al). In controls, none of the monoclonal antibodies to phosphorylated NF stained the perikaryon of neurons. In contrast, in animals treated with Al, all neuronal perikarya containing Al-induced neurofilament bundles (NB) and some lacking well-formed NB immunoreacted with two of the five antibodies to phosphorylated NF. Axons were stained by all five antibodies to phosphorylated NF in both control and Al-treated animals. A broadly reacting monoclonal antibody to a nonphosphorylated NF epitopes immunoreacted with neuronal cell bodies, dendrites and axons in control and Al-intoxicated animals regardless of the presence of Al-induced NB. Staining of Al-induced NB with one of the antibodies to phosphorylated NF was greatly diminished after treatment of sections with trypsin and phosphatase. It is concluded that NF which compose the Al-induced NB have different immunocytochemical characteristics from those of the NF present in the perkaryon of normal neurons. It is likely that, contrary to normal perikaryal NF, NF of Al-induced NB are phosphorylated. Moreover, phosphorylation of NF of Al-induced NB is probably abnormal, since NF of Al-induced NB have immunostaining characteristics different from NF of normal axons. Al-induced NB may result from abnormal phosphorylation of NF in the perikaryon, preventing normal axonal transport of these structures.

Key words

Aluminium Neurofibrillary tangles Phosphorylated neurofilaments 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Bizzi A, Crane RC, Autilio-Gambetti L, Gambetti P (1984) Aluminium effect on slow axonal transport: a novel impairment of neurofilament transport. J Neurosci 4:722–731Google Scholar
  2. Cork LC, Sternberger NH, Sternberger LA, Casanova MF, Struble RG, Price DL (1986) Phosphorylated neurofilament antigens in neurofibrillary tangles in Alzheimer's disease. J Neuropathol Exp Neurol 45:56–64Google Scholar
  3. Gambetti P, Autilio-Gambetti L, Papasozomenos Sch (1981) Bodian's silver method stains neurofilament polypeptides. Science 213:1521–1522Google Scholar
  4. Hirano A (1982) Aspects of the ultrastructure of amyotrophic lateral sclerosis. In: Rowland LP (ed) Human Motor Neuron Disease. Raven Press, New York, pp 75–88Google Scholar
  5. Hirano A, Donnenfeld H, Sasaki S, Nakano I (1984) Fine structural observations of neurofilamentous changes in amyotrophic lateral sclerosis. J Neuropathol Exp Neurol 43:461–470Google Scholar
  6. Sternberger LA (1979) Immunocytochemistry, 3rd edn. John Wiley & Sons, New YorkGoogle Scholar
  7. Sternberger LA, Sternberger NH (1983) Monoclonal antibodies distinguish phosphorylated forms of neurofilaments in situ. Proc Natl Acad Sci USA 80:6126–6130Google Scholar
  8. Sternberger LA, Sternberger NH, Ulrich J (1985) Aberrant neurofilament phosphorylation in Alzheimer disease. Proc Natl Acad Sci USA 82:4274–4276Google Scholar
  9. Troncoso JC, Price DL, Griffin JW, Parhad IM (1982) Neurofibrillary axonal pathology in aluminium intoxication. Ann Neurol 12:278–283Google Scholar

Copyright information

© Springer-Verlag 1986

Authors and Affiliations

  • A. Bizzi
    • 1
  • P. Gambetti
    • 1
  1. 1.Division of Neuropathology, Institute of PathologyCase Western Reserve UniversityClevelandUSA

Personalised recommendations