Skip to main content
Log in

Neurofibrillary tangle predominant form of senile dementia of Alzheimer type: a rare subtype in very old subjects

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

Abstract

In a consecutive autopsy series of 580 demented elderly subject, 256 with the clinical diagnosis of probable/possible Alzheimer's disease (AD), there were 10 cases aged between 80 and 99 years with moderate to severe dementia or confusional state in which neuropathological studies revealed abundant neurofibrillary tangles with predominant involvement of the allocortex (entorhinal region, subiculum, CA 1 sector of hippocampus, amygdala) but no or only very few senile plaques. Small numbers of diffuse deposits of βA4 amyloid protein were present in the entorhinal cortex of 3 and in the isocortex of 5 brains, while neuritic plaques were totally absent. Only a few cases of this “senile dementia with tangles only” or, more correctly, “neurofibrillary predominant type of AD” corresponding to the limbic stage of neuritic AD pathology have been described in the literature. This rare subtype occurring in very old (over 80 years of age) subjects that does not fall within the currently used neuropathological criteria for diagnosis of AD warrants further clinico-pathological documentation.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Arriagada PV, Growdon JH, Hedley-Whyte T, Hyman BT (1992) Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer's disease. Neurology 42:631–639

    Google Scholar 

  2. Bancher C, Grundke-Iqbal K, Fried VA, Smith HT Wisniewski HM (1991) Abnormal phosphorylation of tau precedes ubiquination of neurofibrillary pathology of Alzheimer's disease. Brain Res 539:11–18

    Google Scholar 

  3. Bancher C, Braak H, Fischer P, Jellinger K (1993) Neuropathological staging of Alzheimer lesions and intellectual status in Alzheimer's and Parkinson's disease. Neurosci Lett 162:179–182

    Google Scholar 

  4. Berg L, McKee DW, Miller JP, Barty J, Morris JC (1993) Neuropathological indices of Alzeimer's disease in demented and nondemented persons aged 80 years and older. Arch Neurol 50:349–358

    Google Scholar 

  5. Bouras C, Hof PR, Morrison JH (1993) Neurofibrillary tangle densities in the hippocampal formation in a non-demented population define subgroups of patients with differential early pathologic changes. Neurosci Lett 153:131–135

    Google Scholar 

  6. Braak H, Braak E (1991) Neuropathological staging of Alzheimer-related changes. Acta Neuropathol 82:239–259

    Google Scholar 

  7. Braak H, Braak E (1994) Pathology of Alzheimer's disease. In: Calne DB (ed) Neurodegenerative disease. Saunders, Philadelphia, pp 585–613

    Google Scholar 

  8. Braak H, Duyckaerts C, Braak E, Piette F (1993) Neuropathological staging of Alzheimer-related changes correlates with psychometrically assessed intellectual status. In: Corain B et al (eds) Alzheimer's disease. Advances in clinical and basic research, Wiley, Chichester, pp 131–137

    Google Scholar 

  9. Braak H, Braak E, Mandelkow EM (1994) A sequence of cytoskeleton changes related to the formation of neurofibrillary tangles and neuropil threads. Acta Neuropathol 87:554–567

    Google Scholar 

  10. Braak H, Braak E, Yilzamer D, DeVos RAI, Jansen ENH, Bohl J, Jellinger K (1994) Amygdala pathology in Parkinson's disease. Acta Neuropathol 88:493–500

    Google Scholar 

  11. Chui HC, Tierney M, Zarow C, Lewis A, Sobel E, Perlmutter LS (1993) Neuropathologic diagnosis of Alzheimer disease: interrater reliability in the assessment of senile plaques and neurofibrillary tangles. Alzheimer Dis Assoc Disord 7:48–54

    Google Scholar 

  12. Crystal HA, Dickson DW, Sliwinski MJ, Lipton RB, Grober E, Marks-Nelson H, Antis P (1993) Pathological markers associated with normal aging and dementia in the elderly. Ann Neurol 34:566–573

    Google Scholar 

  13. Davis PB, White H, Price JL, McKeel D, Robins LN (1991) Retropective postmortem dementia assessment. Validation of a new clinical interview to assist neuropathologic study. Arch Neurol 48:613–617

    Google Scholar 

  14. Delacourte A (1993) The pathophysiological basis of Alzheimer's disease. Therapie 48:177–183

    Google Scholar 

  15. Delaere P, Duyckaerts C, He Y, Piette F, Hauw JJ (1991) Subtypes and differential laminar distributions of βA4 deposits in Alzheimer's disease: relationship with the intellectural status of 26 cases. Acta Neuropathol 81:328–335

    Google Scholar 

  16. Delaere P, He Y, Fayet G, Duyckaerts C, Hauw JJ (1993) β-A4 deposits are constant in the brain of the oldest old. Neurobiol Aging 14:191–194

    Google Scholar 

  17. Dickson DW, Crystall HA, Mattiace LA, Masur DM, Blau AD, Davies P, Yen SH, Aronson MK (1991) Identification of normal and pathological aging in prospectively studied nondemented elderly humans. Neurobiol Aging 13:179–189

    Google Scholar 

  18. Dickson DW, Davies P, Bevona C, Van Hoeven KH, Factor SM, Grober E, Aronson MK, Crystal HA (1994) Hippocampal sclerosis: a common pathological feature of dementia in very old (>= 80 years of age) humans. Acta Neuropathol 88:212–221

    Google Scholar 

  19. Duyckaerts C, Delaere P, Hauw JJ (1990) Rating of the lesions in senile dementia of the Alzheimer type: concordance between laboratories. J Neurol Sci 97:293–323

    Google Scholar 

  20. Folstein MF, Folstein SE, McHugh PR (1975) “Mini-Mental State”: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189–198

    Google Scholar 

  21. Giannakopoulos P, Hof PR, Surini M, Michell JP, Bouras C (1993) Quantitative immunohistochemical analysis of the distribution of neurofibrillary tangles and senile plaques in the cerebral cortex of nonagenarian and centenarians. Acta Neuropathol 85:602–610

    Google Scholar 

  22. Goedert M (1993) Tau protein and the neurofibrillary pathology of Alzheimer's disease. Trends Neurosci 16:460–465

    Google Scholar 

  23. Goodman L (1953) Alzheimer's disease. A clinico-pathologic analysis of twenty-three cases with a theory on pathogenesis. J Ment Nerv Dis 117:97–130

    Google Scholar 

  24. Hansen LA, Masliah E, Galasko D, Terry RD (1993) Plaqueonly Alzheimer disease is usually the Lewy body variant and vice versa. J Neuropathol Exp Neurol 52:648–654

    Google Scholar 

  25. Hauw JJ, Vignole P, Duyckaerts C (1986) Etude neuropathologique de douze centenaires. Rev Neurol (Paris) 142:107–115

    Google Scholar 

  26. Heyner RF, Wong-Riley MTT (1992) Entorhinal cortex of the human, monkey and rat: metabolic map as revealed by cytochrome oxidase. J Comp Neurol 326:451–469

    Google Scholar 

  27. Hof PR, Morrison JH (1994) The cellular basis of cortical disconnection in Alzheimer disease and related dementing conditions. In: Terry RD, Katzmann R, Bick KL (eds) Alzheimer disease. Raven Press, New York, pp 197–229

    Google Scholar 

  28. Honer WG, Dickson DW, Gleeson J, Davies P (1992) Regional synpatic pathology in alzheimer's disease. Neurobiol Aging 13:375–382

    Google Scholar 

  29. Hyman BT, Gomeszista T (1994) Alzheimer's disease is a laminar, regional, and neural system specific disease, not a global brain disease. Neurobiol Aging 15:353–355

    Google Scholar 

  30. Hyman BT, Van Hoesen GW, Kromer LJ, Damasio AR (1986) Perforant pathway changes and the memory impairment in Alzheimer disease. Ann Neurol 20:37–40

    Google Scholar 

  31. Hyman BT, Van Hoesen GW, Damasio AR (1990) Memoryrelated neuronal systems in Alzheimer's disease: an anatomic study. Neurology 40:1721–1730

    Google Scholar 

  32. Iwatsubo T, Hasegawa M, Ihara Y (1994) Neuronal and glial tau-positive inclusions in diverse neurologic disease share common phosphorylation characteristics. Acta Neuropathol 88:129–136

    Google Scholar 

  33. Jellinger K, Braak H, Braak E, Fischer P (1991) Alzheimer lesions in the entorhinal region and isocortex in Parkinson's and Alzheimer's disease. Ann NY Acad Sci 640:203–209

    Google Scholar 

  34. Jones RSG (1993) Entorhinal-hippocampal connections: a speculative view of their function. Trends Neurosci 16:58–64

    Google Scholar 

  35. Kazee AM, Eskin TA, Lapham LW, Gabriel RR, McDaniel RD, Hamill RW (1993) Clinicopathologic correlates in Alzheimer's disease — assessment of clinical and pathologic diagnostic criteria. Alzheimer Dis Assoc Disord 7: 152–164

    Google Scholar 

  36. Khachaturian ZS (1985) Diagnosis of Alzheinmer's disease. Arch Neurol 42: 1097–1105

    Google Scholar 

  37. Lassmann H, Weiler R, Fischer P, Bancher C, Jellinger K (1992) Synaptic pathology in Alzheimer's disease: immunological data for markers of synaptic and large dense core vesicles. Neuroscience 46: 1–8

    Google Scholar 

  38. Mukaetova-Ladinsky EB, Harrington CR, Roth M, Wischik CM (1993) Biochemical and anatomical redistribution of tau protein in Alzheimer's disease. Am J Pathol 143: 565–578

    Google Scholar 

  39. Mc Kee AC, Kosik KS, Kowall NW (1992) Neuritic pathology and dementaia in Alzheimer's disease. Ann Neurol 30: 156–165

    Google Scholar 

  40. Mc Keel DW, Ball MJ, Price JL, Smith DS, Miller JP, Berg L, Morris JC (1993) Interlaboratory histopathologic assessment of Alzheimer neuropathology — different methodologies yield comparable diagnostic results. Alzheimer Dis Assoc Disord 7: 136–151

    Google Scholar 

  41. McKhann GD, Drachmann DA, Folstein MF et al (1984) Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of the Department of Health and Human Sevices Task Force on Alzheimer's Disease. Neurology 34: 939–944

    Google Scholar 

  42. Mena R, Wischik CM, Novak M, Milstein C, Cuello AC (1991) A progressive deposition of paired helical filaments (PHF) in the brain characterizes the evolution of dementia in Alzheimer's disease. J Neuropathol Exp Neurol 50: 474–490

    Google Scholar 

  43. Mirra SS, Heyman A McKeel D Sumi SM, Crain BJ, Brownlee LM, Vogel FS, Hughes JP, Van Belle G, Berg L (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 

  44. Mirra SS, Gearing M, McKeel DW, Crain BJ, Hughes JP, Van Belle G, Heyman A, (1994) Interlaboratory comparison of neuropathology assessment in Alzheimer's disease: a study of the consortium to establish a registry for Alzheimer's disease (CERAD). J Neuropathol Exp Neurol 53: 303–315

    Google Scholar 

  45. Mizutani T, Amano N, Sasaki H (1990) Senile dementia of Alzheimer type characterized by laminar neuronal loss exclusively in the hippocampus, parahippocampus and medial occipital cortex Acta Neuropathol 80: 575–580

    Google Scholar 

  46. Mizutani T, Shimada H (1992) Neuropathological background of twenty-seven centenarian brains. J Neurol Sci 108: 168–177

    Google Scholar 

  47. Morris JC, McKeel DWJr, Storandt M, Rubin EM, Price JL, Grant EA, Ball MJ, Berg L (1991) Very mild Alzheimer's disease: informant-based clinical, psychometric, and pathological distinction from normal aging. Neurology 41: 469–478

    Google Scholar 

  48. Paulus W, Bancher C, Jellinger K, (1992) Interrater reliability in the neuropathologic diagnosis of Alzheimer's disease. Neurology 42: 329–332

    Google Scholar 

  49. Price JL, Davis PB, Morris JC, White DL (1992) The distribution of tangles, plaques and related immnohistochemical markers in healthy aging and Alzheimer's disease. Neurobiol Aging 12: 295–312

    Google Scholar 

  50. Reusche E (1991) Silver staining of senile plaques and neurofibrillary tangles in paraffine sections. Pathol Res Pract 187: 1045–1049

    Google Scholar 

  51. Roberts GW, Nash M, Ince PG, Roystom MC, Gentleman SM (1993) On the origin of Alzheimer's disease: a hypothesis. Neuroreport 4: 7–9

    Google Scholar 

  52. Scheff SW, Price DA (1993) Synapse loss in the temporal lobe in Alzheimer's disease. Ann Neurol 33: 190–199

    Google Scholar 

  53. Schnitzler JG (1911) Zur Abgrenzung der sogenanten Alzheimer'schen Krankheit. Z Ges Neurol Psychiatr 7: 34–37

    Google Scholar 

  54. Scott SA, DeKosky ST, Sparks DL, Knox CA, Scheff SW (1992) Amygdala cell loss and atrophy in Alzheimers disease. Ann Neurol 32: 555–563

    Google Scholar 

  55. Sparks DL, Liu H, Scheff SW et al (1993) Temporal sequence of plaque formation in the cerebral cortex of nondemented individuals. J Neuropathol Exp Neurol 52: 135–142

    Google Scholar 

  56. Terry RD, Hansen LA, DeTeresa R, Davies P, Tobias H, Katzman R (1987) Senile dementia of the Alzheimer type without neocortical neurofibrillary tangles. J Neuropathol Exp Neurol 46: 262–268

    Google Scholar 

  57. Terry RD, Masliah E, Hansen LA (1994) Structural basis of the cognitive alteractions in Alzheimer's disease. In: Terry RD, Katzmann R, Bick KL (eds) Alzheimer disease. Raven Press, New York pp 179–196

    Google Scholar 

  58. Tierney MC, Fischer H, Lewis AJ, et al (1988) The NINCDS-ADRDA Work Group criteria for the clinical diagnosis of probable Alzheimer's disease: clinicopathological study of 57 cases. Neurology 38: 356–364

    Google Scholar 

  59. Ulrich J, Spillantini MG, Godert M, Dukas L, Stähelin HB (1992) Abundant neurofibrillary tangles without senile plaques in a subset of patients with senile dementia. Neurodegeneration 1: 257–284

    Google Scholar 

  60. Van Hoesen GW, Hyman BT, Damasio AR (1991) Entorhinal cortex pathology in Alzheimer's disease. Hippocampus 1: 1–8

    Google Scholar 

  61. Vereecken THLG, Vogels OJM, Nieuwenhuys R (1994) Neuron loss and shrinkage in the amygdala in Alzheimer's disease. Neurobiol Aging 15: 45–54

    Google Scholar 

  62. Wisniewski K, Jervis GA, Moretz RC, Wisniewski HM (1979) Alzheimer neurofibrillary tangles in diseases other than senile and presenile dementia. Ann Neurol 5: 288–294

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bancher, C., Jellinger, K.A. Neurofibrillary tangle predominant form of senile dementia of Alzheimer type: a rare subtype in very old subjects. Acta Neuropathol 88, 565–570 (1994). https://doi.org/10.1007/BF00296494

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00296494

Key words

Navigation