Acta Neuropathologica

, Volume 86, Issue 3, pp 265–274

Neurofibrillary tangles of Guamanian amyotrophic lateral sclerosis, parkinsonism-dementia and neurologically normal Guamanians contain a 4-to 4.5-kilodalton protein which is immunoreactive to anti-amyloid β/A4-protein antibodies

  • D. C. Guiroy
  • M. Mellini
  • M. Miyazaki
  • C. Hilbich
  • J. Safar
  • R. M. Garruto
  • R. Yanagihara
  • K. Beyreuther
  • D. C. Gajdusek
Regular Papers

DOI: 10.1007/BF00304141

Cite this article as:
Guiroy, D.C., Mellini, M., Miyazaki, M. et al. Acta Neuropathol (1993) 86: 265. doi:10.1007/BF00304141

Summary

Neurofibrillary tangles (NFT), one of the neurodegenerative features of Alzheimer's disease, Down's syndrome and normal aging, is a constant, widespread neuropathological finding in Guamanian amyotrophic lateral sclerosis (ALS), parkinsonism-dementia (PD) and in neurologically normal Guamanians, dying of causes other than ALS and PD. NFT in brain tissue sections of patients with Guamanian ALS and PD were immunoreactive to antibodies directed against a 43-amino acid synthetic peptide homologous to amyloid β/A4-protein (anti-SP43) associated with Alzheimer's disease. NFT extracted from frozen brain tissues of Guamanian patients with ALS and PD and from tissues of neurologically normal Guamanians were congophilic and birefringent. By negative-stain electron microscopy, NFT preparations contained bundles and/or isolated single, straight, unpaired filaments in Guamanian AlS and occasionally pairing of filaments in neurologically normal Guamanians, measuring 5–20 nm in diameter. Formic acid digestion of NFT preparations, followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and size-exclusion high-pressure liquid chromatography, showed a protein with an apparent molecular mass of 4-to 4.5-kDa, which by Western blot analysis was immunoreactive to anti-SP43. Immunoabsorption of purified NFT or SP43 with anti-SP43 abolished immunostaining. Our study corroborate previous data that amyloid β/A4-protein is present in NFT in Guamanian PD. Furthermore, our data indicate that amyloid β/A4-protein is present in NFT in brain tissues of patients with Guamanian ALS and in neurologically normal Gumananians, suggesting a common mechanism of amyloidogenesis with NFT formation in Alzheimer's disease and normal brain aging.

Key words

Alzheimer's diseaseDown's syndromePaired helical filamentsStraight filaments

Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • D. C. Guiroy
    • 1
  • M. Mellini
    • 2
  • M. Miyazaki
    • 1
  • C. Hilbich
    • 3
  • J. Safar
    • 1
  • R. M. Garruto
    • 1
  • R. Yanagihara
    • 1
  • K. Beyreuther
    • 3
  • D. C. Gajdusek
    • 1
  1. 1.Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and StrokeNational Institutes of HealthBethesdaUSA
  2. 2.Chemical Synthesis and Analysis LaboratoryProgram Resources, Inc.FrederickUSA
  3. 3.Center for Molecular BiologyUniversity of Heidelberg (ZMBH)HeidelbergGermany
  4. 4.Department of NeurologyUniversity of DüsseldorfDüsseldorfGermany
  5. 5.School of MedicineKyushu UniversityFukuokaJapan