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Immunoreactivity profile of hippocampal CA2/3 neurites in diffuse Lewy body disease

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Abstract

Ubiquitin-immunoreactive dystrophic neurites in the CA2/3 region of the hippocampus are characteristic of diffuse Lewy body disease (DLBD). The origin of dystrophic CA2/3 neurites is unknown, but their extent correlates with the number of cortical Lewy bodies (LBs). To examine the molecular composition of these lesions, hippocampal sections were obtained at postmortem from cases of DLBD, Parkinson's disease and Alzheimer's disease. The tissue samples were fixed in a variety of fixatives and immunostained with antibodies to ubiquitin, ubiquitin C-terminal hydrolase (PGP9.5), neurofilament protein subunits, tau protein, paired helical filaments and tyrosine hydroxylase (TH). In addition to being ubiquitin positive, both cortical LBs and CA2/3 dystrophic neurites were positive with a neurofilament monoclonal antibody (RM032) and PGP9.5; however, fewer lesions were detected with these antibodies compared to ubiquitin immunocyto-chemistry. The dystrophic CA2/3 neurites were not stained with antibodies to tau proteins, paired helical filaments or TH. Absence of TH immunoreactivity suggests that CA2/3 neuritic processes are not derived from brain stem dopaminergic afferents to the hippocampus. Since CA2/3 neurites are immunologically similar to cortical LB, the pathogenesis of these lesions may be similar. Characterization of dystrophic CA2/3 neurites and cortical LBs may clarify how these lesions contribute to the emergence of dementia in DLBD.

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References

  1. Arai H, Lee VM-Y, Hill WD, Greenberg BD, Trojanowski JQ (1992) LBs contain beta-amyloid precursor proteins of Alzheimer's disease. Brain Res 585: 386–390

    Google Scholar 

  2. Bancher C, Lassmann H, Budka H, Jellinger K, Grundke-Iqbal I, Iqbal K, Wiche G, Seitelberger F, Wisniewski HM (1989) An antigenic profile of LBs: immunocytochemical indication for protein phosphorylation and ubiquitination. J Neuropathol Exp Neurol 1989. 48: 81–93

    Google Scholar 

  3. Bischoff S (1986) Mesohippocampal dopamine system: characterization, functional and clinical implications. In: Isaacson AL, Pribram KH (eds) The hippocampus, vol. 3 Plenum Press, New York, pp 1–32

    Google Scholar 

  4. Burkhardt CR, Filley CM, Kleinschmidt-DeMasters BK, de la Monte S, Norenberg MD, Schneck SA (1988) Diffuse Lewy body disease and progressive dementia. Neurology 38: 1520–1528

    Google Scholar 

  5. Byrne EJ, Lennox G, Lowe J, Godwin-Austen RB (1989) Diffuse Lewy body disease: clinical features in 15 cases. J Neurol Neurosurg Psychiatry 52: 709–717

    Google Scholar 

  6. Crystal H, Dickson DW, Lizardi JE, Davies P, Wolfson LI (1990) Antemortem diagnosis of diffuse Lewy body disease. Neurology 40: 1523–1528

    Google Scholar 

  7. De Keyser J, Herregodts P, Eliinger G (1990) The mesoneocortical dopamine neuron system. Neurology 40: 1660–1662

    Google Scholar 

  8. Dickson DW, Davies P, Mayeux R, Crystal HA, Thompson D, Goldman JE (1987) Diffuse Lewy body disease: neuropathological and biochemical studies of six patients. Acta Neuropathol (Berl) 75: 8–15

    Google Scholar 

  9. Dickson DW, Crystal H, Mattiace LA, Kress Y, Schwagerl A, Davies P, Yen S-H (1989) Diffuse Lewy body disease: light and electron microscopic immunocytochemistry of senile plaques. Acta Neuropathol 78: 572–584

    Google Scholar 

  10. Dickson DW, Ruan D, Crystal H, Mark MH, Davies P, Kress Y, Yen S-H (1991) Hippocampal degeneration differentiates diffuse Lewy body disease (DLBD) from Alzheimer's disease: light and electron microscopic immunocytochemistry of CA23 neurites specific to DLBD. Neurology 41: 1402–1409

    Google Scholar 

  11. Dickson DW, Wu E, Crystal HA, Mattiace LA, Yen S-H, Davies P (1992) Alzheimer and age-related pathology in diffuse Lewy body disease. In: Boller F, Forcette F, Khachaturian Z, Poncet M, Christen Y (eds) Heterogeneity of Alzheimer's disease. Springer-Verlag Berlin Heidelberg New York Tokyo, pp 168–186

    Google Scholar 

  12. Dickson DW, Crystal HA, Mattiace LA, Masur DM, Blau AD, Davies P, Yen S-H, Aronson MK (1992) Identification of normal and pathological aging in prospectively studied nondemented elderly humans. Neurobiol Aging 13: 179–189

    Google Scholar 

  13. Eggertson DE, Sima AAF (1986) Dementia with cerebral LBs: a mesocortical dopaminergic defect? Arch Neurol 43: 524–527

    Google Scholar 

  14. Forno LS, Sternberger LA, Sternberger NH, Strefling AM, Swanson K, Eng LF (1986) Reaction of LBs with antibodies to phosphorylated and nonphosphorylated neurofilaments. Neurosci Lett 64: 253–258

    Google Scholar 

  15. Galloway PG, Grundke-Iqbal I, Iqbal K, Perry G (1988) LBs contain epitopes both shared and distinct from Alzheimer neurofibrillary tangles. J Neuropathol Exp Neurol 47: 654–663

    Google Scholar 

  16. Gaspar P, Berger B, Febvret A, Vigny A, Krieger-Poulet M, Borri-Voltattorni C (1987) Tyrosine hydroxylase-immunoreactive neurons in the human cerebral cortex: a novel catecholaminergic group? Neurosci Lett 80: 257–262

    Google Scholar 

  17. Gentleman SM, Williams B, Royston MC, Jagoe R, Clinton J, Perry RH, Ince PG, Allsop D, Polak JM, Roberts GW (1992) Quantification of βA4 protein deposition in the medial temporal lobe: a comparison of Alzheimer's disease and senile dementia of the Lewy body type. Neurosci Lett 142: 9–12

    Google Scholar 

  18. Gibb WRG, Esiri MM, Lees AJ (1987) Clinical and pathological features of diffuse cortical Lewy body disease (Lewy body dementia). Brain 110: 1131–1153

    Google Scholar 

  19. Goldman JE, Yen S-H, Chiu F-C, Peress NS (1983) LBs of Parkinson's disease contain neurofilament antigens. Science 221: 1082–1084

    Google Scholar 

  20. Greenberg SG, Davies P (1990) A preparation of Alzheimer paired helical filaments that displays distinct τ proteins by polyacrylamide gel electrophoresis. Proc Natl Acad Sci USA 87: 5827–5831

    Google Scholar 

  21. Haltia M, Ghiso J, Wisniewski T, Kiuru S, Miller D, Frangione B (1991) Gelsolin variant and amyloid co-occur in a case of Alzheimer's with LBs. Neurobiol Aging 12: 313–316

    Google Scholar 

  22. Hansen L, Salmon D, Galasko D, Masliah E, Katzman R, DeTeresa R, Thal L, Pay MM, Hofstetter R, Klauber M, Rice V, Butters N, Alford M (1990) Lewy body variant of Alzheimer's disease: a clinical and pathological entity. Neurology 40: 1–8

    Google Scholar 

  23. Hill WD, Lee VM-Y, Hurtig HI, Murray JM, Trojanowski JQ (1991) Epitopes located in spatially separate domains of each neurofilament subunit are present in Parkinson's disease LBs. J Comp Neurol 309: 150–160

    Google Scholar 

  24. Hughes AJ, Daniel SE, Kilford L, Lees AJ (1992) Accuracy of clinical diagnoses of idiopathic Parkinson's disease: a clinicopathological study of 100 cases. J Neurol Neurosurg Psychiatry 55: 181–184

    Google Scholar 

  25. Ince P, Irving D, MacArthur F, Perry RH (1991) Quantitative neuropathological study of Alzheimer-type pathology in the hippocampus: comparison of senile dementia of Alzheimer type, senile dementia of Lewy body type, Parkinson's disease and nondemented elderly control patients. J Neurol Sci 106: 142–152

    Google Scholar 

  26. Kosaka K, Yoshimura M, Ikeda K, Budka H (1984) Diffuse type of Lewy body disease: progressive dementia with abundant cortical LBs and senile changes of varying degree. A new disease? Clin Neuropathol 3: 185–192

    Google Scholar 

  27. Kosaka K, Tsuchiya K, Yoshimura M (1988) Lewy body disease with and without dementia: a clinicopathologic study of 35 cases. Clin Neuropathol 7: 299–305

    Google Scholar 

  28. Kosik K, Joachim CL, Selkoe DJ (1986) Microtubule associated proteins tau (τ) is a major component of paired helical filaments in Alzheimer's disease. Proc Natl Acad Sci USA 83: 4044–4048

    Google Scholar 

  29. Kukulis RO, Martin-Vasallo P, Peress NS (1989) LBs in tyrosine hydroxylase synthesizing neurons of the human cerebral cortex. Neurosci Lett 106: 49–54

    Google Scholar 

  30. Kuzuhara S, Mori H, Izumiyama N, Yoshimura M, Ihara Y (1988) LBs are ubiquitinated: a light and electron microscopic immunocytochemical study. Acta Neuropathol (Berl) 75: 345–353

    Google Scholar 

  31. Kwak S, Masaki T, Ishiuri S, Sugita H (1991) Multicatalytic proteinase is present in LBs and neurofibrillary tangles in diffuse Lewy body disease brains. Neurosci Lett 128: 21–24

    Google Scholar 

  32. Lee VM-Y, Balin BJ, Otvos L, Torjanowski JQ (1991) A68: a major subunit of paired helical filaments and derivatized froms of normal tau. Science 231: 675–678

    Google Scholar 

  33. Lewis DA, Campbel MJ, Foote SL, Morrison JH (1986) The monoaminergic innervation of primate neocortex. Hum Neurobiol 5: 181–188

    Google Scholar 

  34. Love S, Saitoh T, Quijada S, Cole GM, Terry RD (1988) Alz-50, ubiquitin and tau immunoreactivity of neurofibrillary tangles, Pick bodies and LBs. J Neuropathol Exp Neurol 47: 393–405

    Google Scholar 

  35. Lowe J, Blanchard A, Morrell K (1988) Ubiquitin is a common factor in intermediate filament inclusion bodies of diverse type in man, including those of Parkinson's disease, Pick's disease and Alzheimer's disease, as well as Rosenthal fibers in cerebellar astrocytomas, cytoplasmic bodies in muscle and Mallory bodies in alcoholic liver disease. J Pathol 155: 9–15

    Google Scholar 

  36. Lowe J, McDermott H, Landon M, Mayer RJ, Wilkinson KD (1990) Ubiquitin carboxy-terminal hydrolase (PGP9.5) is selectively present in ubiquitinated inclusion bodies characteristic of human neurodegenerative disease. J Pathol 161: 153–160

    Google Scholar 

  37. Manetto V, Perry G, Tabaton M, Mulvihill P, Fried VA, Smith HT, Gambetti P, Autillo-Gambetti L (1988) Ubiquitin is associated with abnormal cytoplasmic filaments characteristic of neurodegenerative disorders. Proc Natl Acad Sci USA 85: 4501–4505

    Google Scholar 

  38. Mark ME, Sage JI, Dickson DW, Schwartz KO, Duvoisin RC (1992) Levodopa nonresponsive Lewy body parkinsonism: clinicopathologic study of two cases. Neurology 42: 1323–1327

    Google Scholar 

  39. Nakashima S, Ikuta F (1984) Tyrosine hydroxylase proteins in LBs of Parkinsonian and senile brains. J Neurosci Res 64: 91–96

    Google Scholar 

  40. Pappolla MA (1986) LBs of Parkinson's disease: immune electron microscopic demonstration of neurofilament antigens in constituent filaments. Arch Pathol Lab Med 110: 1160–1163

    Google Scholar 

  41. Perry RH, Irving D, Blessed G, Fairbairn A, Perry EK (1990) Senile dementia of the Lewy body type: a clinically and neuropathologically distinct form of Lewy body dementia in the elderly. J Neurol Sci 95: 119–139

    Google Scholar 

  42. Pollanen MS, Bergeron C, Weyer L (1992) Detergentinsoluble Lewy body fibrils share epitopes with neurofilament and tau. J Neurochem 58: 1953–1956

    Google Scholar 

  43. Pollanen MS, Bergeron C, Weyer L (1993) Deposition of detergent-resistent neurofilaments into Lewy body fibrils. Brain Res 603: 121–124

    Google Scholar 

  44. Pollanen MS, Dickson DW, Bergeron C (1993) Pathology and biology of the Lewy body. J Neuropathol Exp Neurol 52: 183–191

    Google Scholar 

  45. Schmidt ML, Lee VM-Y, Trojanowski JQ (1991) Comparative epitope analysis of neuronal cytoskeletal proteins in Alzheimer's disease senile plaque neurites and neuropil threads. Lab Invest 64: 352–357

    Google Scholar 

  46. Schmidt ML, Murray JM, Lee VM-Y, Hill WD, Wertkin A, Trojanowski JQ (1991) Epitope map of neurofilament protein domains on cortical and peripheral nervous system LBs. Am J Pathol 139: 53–65

    Google Scholar 

  47. Torack RM, Morris JC (1990) Tyrosine hydroxylase-like (TH) immunoreactivity in human mesolimbic system. Neurosci Lett 116: 75–80

    Google Scholar 

  48. Torack RM, Morris JC (1992) Tyrosine hydroxylase-like (TH) immunoreactivity in Parkinson's disease and Alzheimer's disease. J Neural Transm [Park Dis Dement] 4: 165–171

    Google Scholar 

  49. Wisniewski T, Haltia M, Ghiso J, Frangione B (1991) LBs are immunoreactive with antibodies to gelsolin related amyloid-Finnish type. Am J Pathol 138: 1077–1083

    Google Scholar 

  50. Wolozin BL, Pruchnicki A, Dickson DW, Davies P (1986) A neuronal antigen in the brains of patients with Alzheimer's disease. Science 232: 648–650

    Google Scholar 

  51. Wu E, Lipton RG, Dickson DW (1992) Amyloid angiopathy in diffuse Lewy body disease. Neurology 42: 2131–2135

    Google Scholar 

  52. Yamada T, McGeer PL, McGeer EG (1992) LBs in Parkinson's disease are recognized by antibodies to complement proteins. Acta Neuropathol 84: 100–104

    Google Scholar 

  53. Yoshimura N, Yoshimura I, Asada M, Hayashi S, Fukushima Y, Kudo H (1988) Juvenile Parkinson's disease with widespread LBs in the brain. Acta Neuropathol 77: 213–218

    Google Scholar 

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Authors and Affiliations

  1. Department of Pathology (Neuropathology), Albert Einstein College of Medicine, 1300 Morris Park Avenue, 1046, Bronx, NY, USA

    D. W. Dickson, Meng-Liang Zhao & S. -H. Yen

  2. Department of Pathology, University of Pennsylvania, Philadelphia, PA, USA

    M. L. Schmidt, V. M. -Y. Lee & J. Q. Trojanowski

Authors
  1. D. W. Dickson
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  2. M. L. Schmidt
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  3. V. M. -Y. Lee
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  4. Meng-Liang Zhao
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  5. S. -H. Yen
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  6. J. Q. Trojanowski
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Supported by National Institutes of Health, grant Nos. NIA AG60803, AG09215, AG10124

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Dickson, D.W., Schmidt, M.L., Lee, V.M.Y. et al. Immunoreactivity profile of hippocampal CA2/3 neurites in diffuse Lewy body disease. Acta Neuropathol 87, 269–276 (1994). https://doi.org/10.1007/BF00296742

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  • DOI: https://doi.org/10.1007/BF00296742

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