Skip to main content
SpringerLink
Log in

A comparative study of histological and immunohistochemical methods for neurofibrillary tangles and senile plaques in Alzheimer's disease

  • Regular Papers
  • Published:
Acta Neuropathologica Aims and scope Submit manuscript

Summary

Several studies have demonstrated that the accurate visualization and quantification of pathological lesions in neurodegenerative disorders depend on the reliability of staining methods. In an attempt to gain a better assessment of the density and distribution of the neuropathological markers of Alzheimer's disease, we compared the staining efficiency of a modified thioflavine S protocol for neurofibrillary tangles (NFT) and senile plaques (SP) to different argentic impregnation techniques (Bielchowsky, Gallyas, Globus, Campbell-Switzer-Martin) and to immunohistochemical stainings obtained with two different antibodies against the amyloid β protein A4 and the microtubule-associated tau protein. The modified thioflavine S technique (MTST) detects up to 60% more SP and up to 50% more NFT than the Bielschowsky and Globus methods, respectively. The results obtained with the specific antibodies are comparable to those obtained with the MTST, but these immunotechniques are more expensive and time consuming for routine neuropathological evaluation, and the appropriate antibodies are not always commercially available. Furthermore, the morphological appearance of NFT and SP with MTST is greatly improved when compared to the classical thioflavine S and the increased signal-to-noise ratio between specifically stained structures and background permits an accurate semi-automatic quantification.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Arnold SE, Hyman BT, Flory J, Damasio AR, Van Hoesen GW (1991) The topographical and neuroanatomical distribution of neurofibrillary tangles and neurite plaques in the cerebral cortex of patients with Alzheimer's disease. Cerebral Cortex 1:103–116

    Google Scholar 

  2. Behrouz N, Défossez A, Delacourte A, Hublau P, Mazzuca M (1989) Alzheimer's disease: glycolytic pretreatment dramatically enhances immunolabeling of senile plaques and cerebrovascular amyloid substance. Lab Invest 61:576–580

    Google Scholar 

  3. Benson DF, Davis RJ, Snyder BD (1988) Posterior cortical atrophy. Arch Neurol 45:789–793

    Google Scholar 

  4. Bielschowsky M (1904) Die Silberimprägnation der Neurofibrillen. J Psychol Neurol 3:169–188

    Google Scholar 

  5. Braak H, Braak E, Grundke-Iqbal I, Iqbal K (1986) Occurrence of neuropil threads in the senile human brain and in Alzheimer's disease: a third location of paired helical filaments outside of neurofibrillary tangles and neuritic plaques. Neurosci Lett 65:351–355

    Google Scholar 

  6. Campbell SK, Switzer RC, Martin TL (1987) Alzheimer's plaques and tangles: a controlled and enhanced method. Soc Neurosci Abstr 13:678

    Google Scholar 

  7. Défossez A, Beauvillain JC, Delacourte A, Mazzuca M (1990) Alzheimer's disease: a new evidence for common epitopes between monotubule associated protein tau and paired helical filaments (PHF): demonstration at the electron microscope by a double immunogold labelling. Virchows Arch [A] 413:141–145

    Google Scholar 

  8. Delacourte A, Flament S, Dibe EM, Hublau P, Sablonnière B, Hémon B, Scherrer V, Défossez A (1990) Pathological proteins Tau 64 and 69 are specifically expressed in the somatodendritic domain of the degenerating cortical neurons during Alzheimer's disease. Demonstration with a panel of antibodies against Tau proteins. Acta Neuropathol 80:111–117

    Google Scholar 

  9. Duyckaerts C, Brion JP, Hauw JJ, Flament-Durand J (1987) Quantitative assessment of the density of neurofibrillary tangles and senile plaques in senile dementia of the Alzheimer type. Comparison of immunocytochemistry with a specific antibody and Bodian's protargol method. Acta Neuropathol (Berl) 73:167–170

    Google Scholar 

  10. Duyckaerts C, Delaère P, Hauw JJ, Abbamondi-Pinto AL, Sorbi S, Allen I, Brion JP, Flament-Durand J, Duchen L, Kauss J, Schlote W, Lowe J, Probst A, Ravid R, Swaab DF, Renkawek K, Tomlinson B (1990) Rating of the lesions in senile dementia of the Alzheimer type: concordance between laboratories. A European multicenter study under the auspices of EURAGE. J Neurol Sci 97:295–323

    Google Scholar 

  11. Flament S, Delacourte A, Delaère P, Duyckaerts C, Hauw JJ (1990) Correlation between microscopical changes and tau 64 and 69 biochemical detection in senile dementia of the Alzheimer type. Tau 64 and 69 are reliable markers of the neurofibrillary degeneration. Acta Neuropathol 80:212–215

    Google Scholar 

  12. Gallyas F (1971) Siver staining of Alzheimer's neurofibrillary changes by means of physical development. Acta Morphol Acad Sci Hung 19:1–8

    Google Scholar 

  13. Gentleman SM, Bruton C, Allsop D, Lewis SJ, Polak JM, Roberts GW (1989) A demonstration of the advantages of immunostaining in the quantification of amyloid plaque deposits. Histochemistry 92:355–358

    Google Scholar 

  14. Globus JH (1927) The Cajal and Hortega glia staining methods. Arch Neurol Psychiatry 8:263–271

    Google Scholar 

  15. Golaz J, Bouras C, Hof PR (1991) Motor cortex involvement in presenile dementia: report of a case. J Geriatr Psychiatry Neurol (in press)

  16. Guntern R, Bouras C, Vallet PG, Hof PR (1989) An improved staining method for senile plaques and neurofibrillary tangles in Alzheimer's disease: quantitative comparison with other techniques. Soc Neurosci Abstr 15:1038

    Google Scholar 

  17. Guntern R, Vallet PG, Bouras C, Constantinidis J (1989) An improved immunohistostaining procedure for peptides in human brain. Experientia 45:159–161

    Google Scholar 

  18. Guntern R, Bouras C, Hof PR, Vallet PG (1991) An improved staining method for senile plaques and neurofibrillary tangles in Alzheimer's disease. Experientia (in press)

  19. Hauw JJ, Duyckaerts C, Delaère P (1988) Neuropathology of aging and DAT: how can age-related changes be distinguished from those due to disease processes. In: Henderson AS, Henderson JH (eds) Etiology of dementia of Alzheimer's type. John Wiley & Sons, Chichester, pp 195–211

    Google Scholar 

  20. Henderson VW, Finch CE (1989) The neurobiology of Alzheimer's disease. J Neurosurg 70:335–353

    Google Scholar 

  21. Hof PR, Bouras C (1991) Object recognition deficit in Alzheimer's disease: possible disconnection of the occipitotemporal component of the visual system. Neurosci Lett 122:53–56

    Google Scholar 

  22. Hof PR, Morrison JH (1990) Quantitative analysis of a vulnerable subset of pyramidal neurons in Alzheimer's disease. II. Primary and secondary visual cortex. J Comp Neurol 301:55–64

    Google Scholar 

  23. Hof PR, Bouras C, Constantinidis J, Morrison JH (1989) Balint's syndrome in Alzheimer's disease: specific disruption of the occipito-parietal visual pathway. Brain Res 493:368–375

    Google Scholar 

  24. Hof PR, Bouras C, Constantinidis J, Morrison JH (1990) Selective disconnection of specific visual association pathways in cases of Alzheimer's disease presenting with Balint's syndrome. J Neuropathol Exp Neurol 49:168–184

    Google Scholar 

  25. Hof PR, Cox K, Morrison JH (1990) Quantitative analysis of a vulnerable subset of pyramidal neurons in Alzheimer's disease. I. Superior frontal and inferior temporal cortex. J comp Neurol 301:44–54

    Google Scholar 

  26. Hof PR, Knabe R, Bovier P, Bouras C (1991) Neuropathological observations in a case of autism presenting with self-injury behavior. Acta Neuropathol (in press)

  27. Hof PR, Perl DP, Loerzel AJ, Morrison JH (1991) Neurofibrillary tangles distribution in the cerebral cortex of Parkinson dementia cases from Guam: differences with Alheimer's disease. Brain Res (in press)

  28. Ikeda SI, Allsop D, Glenner GG (1989) Morphology and distribution of plaque and related deposits in the brains of Alzheimer's disease and control cases. Lab Invest 60:113–122

    Google Scholar 

  29. Jagust WJ, Davies P, Tillerborcich JK (1990) Focal Alzheimer's disease. Neurology 40:14–19

    Google Scholar 

  30. Katzman R, Saitoh T (1991) Advances in Alzheimer's disease. FASEB J 5:278–286

    Google Scholar 

  31. Khachaturian ZS (1985) Diagnosis of Alzheimer's disease. Arch Neurol 42:1097–1104

    Google Scholar 

  32. Kim KS, Miller DL, Sapienza VG, Chen CJ, Vai C, Grundke-Iqbal I, Curry JR, Wisniewski HM (1988) Production and characterization of monoclonal antibodies reactive to synthetic cerebrovascular amyloid peptide. Neurosci Res Commun 2:121–130

    Google Scholar 

  33. Lamy C, Duyckaerts P, Delaère P, Payan CH, Fermanian J, Poulain V, Hauw JJ (1989) Comparison of seven staining methods for senile plaques and neurofibrillary tangles in a prospective series of 15 elderly patients. Neuropathol Appl Neurobiol 15:563–578

    Google Scholar 

  34. Lewis DA, Campbell MJ, Terry RD, Morrison JH (1987) Laminar and regional distribution of neurofibrillary tangles and neuritic plaques in Alzheimer's disease: a quantitative study of visual cortex and auditory cortices. J Neurosci 7:1799–1808

    Google Scholar 

  35. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM (1984) Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA work group under the auspices of the Department of health and Human services task Force on Alzheimer's disease. Neurology 34:939–944

    Google Scholar 

  36. Mirra SS, Heyman A, McKeel D, Sumi SM, Crain BJ, Brownlee LM, Vogel FS, Hughes JP, van Belle G, Berg L and CERAD neuropathologists (1991) The Consortium to establish a registry for Alzheimer's disease (CERAD). II. Standardization of the neuropathologic assessment of Alzheimer's disease. Neurology 41:479–486

    Google Scholar 

  37. Mutrux S (1947) Diagnostic différentiel histologique de la maladie d'Alzheimer et de la démence sénile-Pathophobie de la zone de projection corticale. Monatsschr Psychiatr Neurol 113:100–117

    Google Scholar 

  38. Pappola MA, Omar RA, Robakis NK (1991) Immunohistochemical demonstration of antioxidant enzymes in Alzheimer's disease. Am J Pathol (in press)

  39. Pearson RCA, Esiri MM, Hiorns RW, Wilcock GK, Powell TPS (1985) Anatomical correlates of the distribution of the pathological changes in the neocortex in Alzheimer's disease. Proc Natl Acad Sci USA 82:4531–4534

    Google Scholar 

  40. Rogers J, Morrison JH (1985) Quantitative morphology and regional and laminar distributions of senile plaques in Alzheimer's disease. J Neurosci 5:2801–2808

    Google Scholar 

  41. Rudelli RD, Ambler MV, Wisniewski HM (1984) Morphology and distribution of Alzheimer neuritic (senile) and amyloid plaques in striatum and diencephalon. Acta Neuropathol (Berl) 64:273–281

    Google Scholar 

  42. Wilcock GK, Esiri MM (1982) Plaques, tangles and dementia. A quantitative study. J Neurol Sci 56:343–356

    Google Scholar 

  43. Wisniewski HM, Rabe A, Zigman W, Silverman W (1989) Neuropathological diagnosis of Alzheimer disease. J Neuropathol Exp Neurol 48:606–609

    Google Scholar 

  44. Wisniewski HM, Wen GY, Kim KS (1989) Comparison of four staining methods on the detection of neuritic plaques. Acta Neuropathol 78:22–27

    Google Scholar 

  45. Yamaguchi H, Hirai S, Morimatsu M, Shoji M, Harigaya Y (1988) Diffuse type of senile plaques in the brains of Alzheimer-type dementia. Acta Neuropathol 77:113–119

    Google Scholar 

  46. Yamamoto T, Hirano A (1986) A comparative study of modified Bielschowsky, Bodian and thioflavine S stains on Alzheimer's neurofibrillary tangles. Neuropathol Appl Neurobiol 12:3–9

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Psychiatry, University of Geneva, 2 ch. du Petit Bel-Air, CH-1225, Chêne-Bourg (Geneva), Switzerland

    P. G. Vallet, R. Guntern & J. Golaz

  2. Department of Mount Sinai School of Medicine, Fishberg Research Center for Neurobiology, 10029, New York, NY, USA

    P. R. Hof & N. K. Robakis

  3. Department of Geriatrics and Adult Development, Mount Sinai School of Medicine, 10029, New York, NY, USA

    P. R. Hof

  4. Department of Psychiatry, Mount Sinai School of Medicine, 10029, New York, NY, USA

    N. K. Robakis

  5. INSERM U156, Laboratoire de Neurosciences, Place de Verdun, F-59045, Lille, France

    A. Delacourte

Authors
  1. P. G. Vallet
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. Guntern
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P. R. Hof
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. Golaz
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A. Delacourte
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. N. K. Robakis
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. C. Bouras
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Supported in part by the Brookdale Foundation and the American Health Assistance Foundation (to P.R.H.) and the NIH (AG05138 and AGO8200 to N.K.R.)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vallet, P.G., Guntern, R., Hof, P.R. et al. A comparative study of histological and immunohistochemical methods for neurofibrillary tangles and senile plaques in Alzheimer's disease. Acta Neuropathol 83, 170–178 (1992). https://doi.org/10.1007/BF00308476

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00308476

Key words

Search

Navigation