Abstract
A biochemical study was performed to quantify and map the neurodegenerating process in cortical and subcortical brain areas from a case of progressive supranuclear palsy (PSP). Our approach was based on a Western blot analysis of pathological Tau proteins, which are the basic components of neurofibrillary lesions. We found that: (i) the abnormal Tau proteins can be detected in all cortical areas, sometimes in larger amounts than in some subcortical areas; (ii) these abnormal Tau proteins consist of a doublet called Tau 64 and 69, except for in the entorhinal cortex where we detected, as for Alzheimer brains, the triplet of Tau proteins called Tau 55, 64 and 69; (iii) the amounts of abnormal Tau proteins were higher in some neocortical regions, especially in the frontal lobe, than in the hippocampal formation. Our results show that the neocortical pathology in PSP, as revealed by the presence of pathological proteins, is more extended than thought so far. Our biochemical approach appears to be more sensitive than the immunohistochemical one and can clearly differentiates between two types of neurofibrillary pathology, the Alzheimer type with a triplet of abnormal Tau proteins (Tau 55, 64 and 69) and the PSP type with a characteristic doublet (Tau 64 and 69).
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Albert ML, Feldman RG, Willis AL (1974) The “subcortical dementia” of progressive supranuclear palsy. J Neurol Neurosurg Psychiatry 37: 121–130
Arnold SE, Hyman BT, Flory J, Damasio AR, Van Hoesen GW (1991) The topographical and neuroanatomical distribution of neurofibrillary tangles and neuritic plaques in the cerebral cortex of patients with Alzheimer's disease. Cerebral Cortex 1: 103–116
Bancher C, Lassman H, Budka H, Grundke-Iqbal I, Iqbal K, Wiche G, Seitelberg F, Wisniewski HM (1987) Neurofibrillary tangles in Alzheimer's disease and progressive supranuclear palsy: antigenic similarities and differences. Microtubule-associated tau proteins is prominent in all types of tangles. Acta Neuropathol (Berl) 74: 39–46
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
Braak H, Braak E (1991) Neuropathological staging of Alzheimer-related changes. Acta Neuropathol 82: 239–259
Braak H, Jellinger K, Braak E, Bohl J (1992) Allocortical neurofibrillary changes in progressive supranuclear palsy. Acta Neuropathol 84: 478–483
Cummings JL, Benson DF (1984) Subcortical dementia: review of an emerging concept. Arch Neurol 41: 874–879
Delacourte A, Flament S, Dibe EM, Hublau P, Sablonnière B Hémon B, Sherrer 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
Flament S, Delacourte A, Hemon B, Defossez A (1989) Characterization of two pathological Tau proteins variants in Alzheimer's brains cortices. J Neurol Sci 92: 133–141
Flament S, Delacourte A, Verny M, Hauw JJ, Javoy-Agid F (1991) Abnormal tau proteins in progressive supranuclear palsy. Similarities and differences with the neurofibrillary degeneration of the Alzheimer type. Acta Neuropathol 81: 591–596
Hauw JJ, Verny M, Delaère P, Cervera P, He Y, Duyckaerts C (1990) Constant neurofibrillary changes in the neocortex in progressive supranuclear palsy. Basic differences with Alzheimer's disease and aging. Neurosci Lett 119: 182–186
Hof PR, Delacourte A, Bouras C (1992) Distribution of cortical neurofibrillary tangles in progressive supranuclear palsy: a quantitative analysis of six cases. Acta Neuropathol 84: 45–51
Ishino H, Otsucki S (1976) Frequency of Alzheimer's neurofibrillary tangles in the cerebral cortex in progressive supranuclear palsy (subcortical argyrophilic dystrophy). J Neurol Sci 28: 309–316
Jellinger K, Riederer P, Tomonaga M (1980) Progressive supranuclear palsy: clinico-pathological and biochemical studies. J Neural Trans [Suppl] 16: 111–128
Laemmli UK (1970) Cleavage of structural proteins during head assembly of bacteriophage T4. Nature 227: 680–685
Maneto M, Perry G, Tabaton M, Mulvihill P, Fried VA, Smith HT, Gambetti P, Autilio-Gambetti L (1988) Ubiquitin is associated with abnormal cytoplasmic filaments characteristic of neurodegenerative diseases. Proc Natl Acad Sci USA 85: 4501–4505
Mann DMA, Oliver R, Snowden JS (1993) The topographic distribution of brain atrophy in Huntington's disease and progressive supranuclear palsy. Acta Neuropathol 85: 553–559
Montpetit V, Clapin DF, Guberman A (1985) Substructure of 20-nm filaments of progressive supranuclear palsy. Acta Neuropathol (Berl) 68: 311–318
Pearson RCA, Esiri MM, Hiorns RW, Wilcock GK, Powell TPS (1985) Anatomical correlates of the distribution of the pathological changes in the neocortex in AD. Proc Nalt Acad Sci USA 82: 4531–4534
Perry G, Rizzuto N, Autilio-Gambetti L, Gambetti P (1985) Paired helical filaments from Alzheimer disease contain cytoskeletal components. Proc Natl Acad Sci USA 82: 3916–3920
Pollock NJ, Mirra SS, Binder LI, Hansen LA, Wood JG (1986) Filamentous aggregates in Pick's disease, progressive supranuclear palsy, and Alzheimer's disease show antigenic determinants with microtubule-associated protein, tau. Lancet 2: 1211
Ruberg M, Javoy-Agid F, Lebalc'h N, Hirsch E, Scatton B, Lheureux R, Hauw JJ, Duyckaerts C, Gray F, Morel-Maroger A, Rascol A, Serdaru M, Agid Y (1985) Dopaminergic and cholinergic lesions in progressive supranuclear palsy. Ann Neurol 18: 523–529
Steele JC, Richardson JC, Olszewski J (1964) Progressive supranuclear palsy. A heterogenous degeneration involving brain stem, basal ganglia and cerebellum with vertical gaze and pseudobulbar palsy, nuchal dystonia and dementia. Arch Neurol 10: 333–359
Tabaton M, Whitehouse PJ, Perry G, Davies P, Autilio-Gambetti L, Gambetti P (1988) Alz 50 recognizes abnormal filaments in Alzheimer's disease and progressive supranuclear palsy. Ann Neurol 24: 407–413
Tellez-Nagel I, Wisniewski HM (1973) Ultrastructure of neurofibrillary tangles in Steele-Richardson-Olszewski syndrome. Arch Neurol 29: 324–327
Tomonaga M (1977) Ultrastructure of neurofibrillary tangles in progressive supranuclear palsy. Acta Neuropathol (Berl) 37: 177–181
Vermersch P, Frigard B, Delacourte A (1992) Biochemical mapping of cortical neurofibrillary degeneration in Alzheimer's disease: constant involvement of limbic areas and rostro-caudal heterogeneity in the neocortex. Acta Neuropathol 85: 48–54
Vermersch P, Frigard B, David JP, Fallet-Bianco C, Delacourte A (1992) Presence of abnormal tau proteins in the entorhinal cortex in aged non-demented subjects. Neurosci Lett 144: 143–146
Yen SH, Horoupian DS, Terry RD (1983) Immunocytochemical comparison of neurofibrillary tangles in senile dementia of Alzheimer type, progressive supranuclear palsy, and postencephalitic parkinsonism. Ann Neurol 13: 172–175
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Supported by ADERMA, CH&U de Lille, and INSERM clinical network CAR 492011, Société Alzheimer du Canada and Fondation de l'Age d'Or du Québec
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Vermersh, P., Wattez, A., Delacourte, A. et al. Biochemical mapping of neurofibrillary degeneration in a case of progressive supranuclear palsy: evidence for general cortical involvement. Acta Neuropathol 87, 572–577 (1994). https://doi.org/10.1007/BF00293317
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DOI: https://doi.org/10.1007/BF00293317