Summary
Immunocytochemistry with monoclonal antibodies to the β-protein and to antigens associated with paired helical filaments (PHF) allows us to selectively stain two major components of neuritic (senile) plaques (NP): PHF and amyloid deposits. Using this method, the structure of NP in the brains of Alzheimer disease victims was compared to their structure in the brains of non-demented aged individuals selected for high numbers of NP. It is demonstrated that the dystrophic neurites participating in the plaque formation contain PHF only when cortical nerve cells in the same brain area form neurofibrillary tangles (NFT). People with many NP and many NFT were always demented, whereas people with many NP but few, if any NFT were not. It is speculated that there is individual susceptibility to the formation of PHF and that their appearance may represent a nonspecific response of the neuronal network to different kinds of injuries, like the deposition of amyloid in Alzheimer disease, or other pathogenic factors associated with various dementive neurodegenerative diseases. It is hypothesized that the deposition of brain amyloid in people resistant to neurofibrillary pathology may induced too little dysfunction for the development of dementia.
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Ball MJ (1988) Hippocampal histopathology — A critical substrate for dementia of the Alzheimer type. Interdiscip Top Gerontol 25:16–37
Bancher C, Brunner C, Lassmann H, Budka H, Jellinger K, Wiche G, Seitelberger F, Grundke-Iqbal I, Iqbal K, Wisniewski HM (1989) Accumulation of abnormally phosphorylated tau precedes the formation of neurofibrillary tangles in Alzheimer's disease. Brain Res 477:90–99
Binder LI, Frankfurter A, Rebhun LI (1985) The distribution of tau in the mammalian central nervous system. J Cell Biol 101:1371–1378
Braak H, Braak E (1988) Neuropil threads occur in dendrites of tangle-bearing nerve cells. Neuropathol Appl Neurobiol 14:39–44
Braak H, Braak E, Grundke-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
Corsellis JAN (1962) Mental illness and the ageing brain. Institute of Psychiatry. Maudsley Monographs, No 9. Oxford University Press
Crystal H, Dickson D, Fuld P, Masur D, Scott R, Mehler M, Masdeu J, Kawas C, Aronson M, Wolfson L (1988) Clinico-pathologic studies in dementia: nondemented subjects with pathologically confirmed Alzheimer's disease. Neurology 38:1682–1687
Dayan AD (1970) Quantitative histological studies on the aged human brain. Acta Neuropathol (Berl) 16:95–102
Dickson DW, Farlo J, Davies P, Crystal H, Fuld P, Yen SH (1988) Alzheimer's disease. A double-labeling immunohistochemical study of senile plaques. Am J Pathol 132:86–101
Doebler JA, Markesbery WR, Anthony A, Davies P, Scheff SW, Rhodes RE (1988) Neuronal RNA in relation to Alz-50 immunoreactivity in Alzheimer's disease. Ann Neurol 23:20–24
Dyrks T, Weidemann A, Multhaup G, Salbaum JM, Lemaire HG, Kang J, Müller-Hill B, Masters CL, Beyreuther K (1988) Identification, transmembrance orientation and biogenesis of the amyloid A4 precursor of Alzheimer's disease. EMBO J 7:949–957
German DC, White CL III, Sparkman DR (1987) Alzheimer's disease: neurofibrillary tangles in nuclei that project to the cerebral cortex. Neuroscience 21:305–312
Grundke-Iqbal I, Iqbal K, Tung Y-C, Quinlan M, Wisniewski HM, Binder LI (1986) Abnormal phosphorylation of the microtubule-associated protein τ (tau) in Alzheimer cytoskeletal pathology. Proc Natl Acad Sci USA 83:4913–4917
Hirano A, Zimmerman HM (1962) Alzheimer's neurofibrillary changes. Arch Neurol 7:227–241
Hirano A, Malamud N, Kurland LT (1961) Parkinsonism-dementia complex, an endemic disease on the Island of Guam. Brain 84:662–679
Hyman BT, Van Hoesen GW, Kromer LJ, Damasio AR (1986) Perforant pathway changes and the memory impairment of Alzheimer's disease. Ann Neurol 20:472–481
Hyman BT, Van Hoesen GW, Wolozin BL, Davies P, Kromer LJ, Damasio AR (1988) Alz-50 antibody recognizes Alzheimer-related neuronal changes. Ann Neurol 23:371–379
Kang J, Lemaire HG, Unterbeck A, Salbaum JM, Masters CL, Grzeschik KH, Multhaup G, Beyreuther K, Müller-Hill B (1987) The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor. Nature 325:733–736
Katzman R, Terry R, DeTeresa R, Brown T, Davies P, Fuld P, Renbing X, Peck A (1988) Clinical, pathological, and neurochemical changes in dementia: a subgroup with preserved mental status and numernous neocortical plaques. Ann Neurol 23:138–144
Kim KS, Miller DL, Sapienza VJ, Chen CM, Bai C, Grundke-Iqbal I, Currie JR, Wisniewski HM (1988) Production and characterization of monoclonal antibodies reactive to synthetic cerebrovascular amyloid peptide. Neurosci Res Commun 2:121–130
Kitamoto T, Ogomori K, Tateishi J, Prusiner S (1987) Methods in laboratory investigation. Formic acid pretreatment enhances immunostaining of cerebral and systemic amyloids. Lab Invest 57:230–236
Ksiezak-Reding H, Binder LI, Yen S-H (1988) Immunochemical and biochemical characterization of tau proteins in normal and Alzheimer's disease brains with Alz 50 and tau-1. J Biol Chem 263:7948–7953
Ksiezak-Reding H, Davies P, Yen S-H (1988) Alz 50, a monoclonal antibody to Alzheimer's disease antigen, crossreacts with tau proteins from bovine and normal human brain. J Biol Chem 263:7943–7947
Love S, Saitoh T, Quijada GM, Terry RD (1988) Alz-50, ubiquitin and tau immunoreactivity of neurofibrillary tangles, Pick bodies and Lewy bodies. J Neuropathol Exp Neurol 47:393–405
Perry G, Mulvihill P, Fried VA, Smith HT, Grundke-Iqbal I, Iqbal K (1989) Immunochemical properties of ubiquitin conjugates in the paired helical filaments of Alzheimer disease. J Neurochem 52:1523–1528
Popovitch ER, Wisniewski HM, Kaufman MA, Grundke-Iqbal I, Wen GY (1987) Young adult-form of dementia with neurofibrillary changes and Lewy bodies. Acta Neuropathol (Berl) 74:97–104
Rasool C, Abraham C, Anderton B, Haugh M, Kahn J, Selkoe DJ (1984) Alzheimer's disease: immunoreactivity of neurofibrillary tangles with anti-neurofilament and antipaired helical filament antibodies. Brain Res 310:249–260
Roth M, Tomlinson BE, Blessed G (1966) Correlation between scores for dementia and counts of senile plaques in cerebral gray matter of elderly subjects. Nature 206:109–110
Scicutella BL, Wolozin BL, Davies P (1987) Alz 50 appears to be able to distinguish between the neuritic plaques of Alzheimers's disease and those of normal aging. Soc Neurosci Abstr 13:1150 [abstr 316.5]
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
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
Wang GP, Grundke-Iqbal I, Kascsak RJ, Iqbal K, Wisniewski HM (1984) Alzheimer neurofibrillary tangles: monoclonal antibodies to inherent antigen(s). Acta Neuropathol (Berl) 62:268–275
Wilcock GK, Esiri MM, Bowen DM, Smith CCT (1982) Alzheimer's disease. Correlation of cortical choline acetyltransferase activity with the severity of dementia and histological abnormalities. J Neurol Sci 57:407–417
Wisniewski HM, Johnson AB, Raine CS, Kay WJ, Terry RD (1970) Senile plaques and cerebral amyloidosis in aged dogs. Lab Invest 23:287–296
Wisniewski HM, Coblentz JM, Terry ED (1972) Pick's disease. A clinical and ultrastructural study. Arch Neurol 26:97–108
Wisniewski HM, Ghetti B, Terry RD (1973) Neuritic (senile) plaques and filamentous changes in aged rhesus monkeys. J Neuropathol Exp Neurol 32:566–584
Wisniewski HM, Narang HK, Corsellis JAN, Terry RD (1976) Ultrastructural studies of the neuropil and neurofibrillary tangles in Alzheimer's disease and post-traumatic dementia. J Neuropathol Exp Neurol 35:367 [abstr]
Wisniewski HM, Moretz RC, Lossinsky AS (1981) Evidence for induction of localized amyloid deposits and neuritic plaques by an infections agent. Ann Neurol 10:517–522
Wisniewski HM, Sinatra RS, Iqbal K, Grundke-Iqbal I (1981) Neurofibrillary and synaptic pathology in the aged brain. In: Johnson JE Jr (ed) Aging and cell structure, vol 1. Plenum Publishing, New York, pp 105–142
Wismewski HM, Vorbrodt AW, Moretz RC, Lossinsky AS, Grundke-Iqbal I (1982) Pathogenesis of neuritic (senile) and amyloid plaque formation. In: Hoyer S (ed) The aging brainphysiological and pathological aspects. Exp Brain Res [Suppl] 5:3–9
Wisniewski HM, Iqbal K, Grundke-Iqbal I, Rubenstein R, Wen GY, Merz PA, Kascsak R, Kristensson K (1986) Amyloid in Alzheimer's disease and unconventional viral infections. Neuropathology [Suppl] 3:87–94
Wisniewski HM, Popovitch ER, Kaufman MA, Wisniewski KE (1987) Neurofibrillary changes in advanced hydrocephalus. A clinicopathological study. J Neuropathol Exp Neurol 46:340 [abstr]
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
Wolozin BL, Davies P (1987) Alzheimer-related neuronal protein A68: specificity and distribution. Ann Neurol 22:521–526
Wolozin BL, Pruchniki A, Dickson DW, Davies P (1986) A neuronal antigen in the brains of Alzheimer patients. Science 232:648–650
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Supported in part by grants AGO-4220 and HD-22634 from the National Institutes of Health
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Barcikowska, M., Wisniewski, H.M., Bancher, C. et al. About the presence of paired helical filaments in dystrophic neurites participating in the plaque formation. Acta Neuropathol 78, 225–231 (1989). https://doi.org/10.1007/BF00687751
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DOI: https://doi.org/10.1007/BF00687751