Summary
We have studied the immunohistochemical reactivity and ultrastructure of both neurofibrillary tangles (NFTs) occurring with severe neurofibrillary diseases, and Pick bodies (PBs) associated with Pick's disease. The NFTs and PBs did not react immunohistochemically with the anti-nonphosphorylated neurofilament monoclonal antibody irrespective of whether they were pretreated with alkaline phosphatase. In granular neurons of the dentate fascia of Ammon's horn in cases of dementia of the Alzheimer type (DAT), NFTs either resembled PB-like inclusion bodies (Horoupian's inclusion bodies) in form, or had a perinuclear structure. Immunohistochemically and ultrastructurally, the NFTs in the dentate fascia in cases of DAT, including Horoupian's inclusion bodies, were similar to the NFTs in the pyramidal neurons of Ammon's horn, which are found most frequently in association with severe neurofibrillary diseases. Under a light microscope, Horoupian's inclusion bodies and PBs could not be differentiated and appeared to be argyrophilic round cytoplasmic inclusions in granular neurons of the dentate fascia. There were, however, ultrastructural differences. Horoupian's inclusion bodies consisted of bundles made up of straight tubules (STs), each about 15 nm in diameter. These bundles were intermixed with a few paired helical filaments which occurred at intervals of about 80 nm. On the other hand, PBs were composed of randomly distributed 15-nm-wide STs, intermixed with a very few fibrillary structures. These fibrils had a periodicity of about 160 nm, and ranged in width from about 15 nm to 30 nm. Horoupian's inclusion bodies associated with DAT and PBs associated with Pick's disease are different in this neuropathological aspect. The NFTs, including Horoupian's inclusion bodies in the dentate fascia in cases of DAT, are considered to be a manifestation of neurofibrillary degeneration.
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References
Brion JP, Couck AM, Passareiro E, Flament-Durand J (1985) Neurofibrillary tangles of Alzheimer's disease: an immunohistochemical study. J Submicrosc Cytol 17:89–96
Brion S, Mikol J, Psimaras A (1973) Recent findings in Pick's disease. Prog Neuropathol 2:421–452
Constantinidis J (1985) Pick dementia: anatomoclinical correlations and pathophysiological considerations. In: Rose FC (ed) Modern approaches to the dementias, part I: etiology and pathophysiology (interdisciplinary topics in gerontology, vol 19). Karger, Basel, pp 72–97
Dickson DW, Kress Y, Crowe A, Yen S-H (1985) Monoclonal antibodies to Alzheimer neurofibrillary tangles. 2. Demonstration of a common antigenic determinant between ANT and neurofibrillary degeneration in progressive supranuclear palsy. Am J Pathol 120:292–303
Dickson DW, Yen S-H, Horoupian DS (1986) Pick bodylike inclusions in the dentate fascia of the hippocampus in Alzheimer's disease. Atta Neuropathol (Berl) 71:38–45
Dickson DW, Yen S-H, Suzuki KI, Davies P, Garcia JH, Hirano A (1986) Ballooned neurons in select neurodegenerative diseases contain phosphorylated neurofilament epitopes. Acta Neuropathol (Berl) 71:216–223
Haugh MC, Probst A, Ulrich J, Kahn J, Anderton BH (1986) Alzheimer neurofibrillary tangles contain phosphorylated and hidden neurofilament epitopes. J Neurol Neurosurg Psychiatry 49:1213–1220
Hirano A, Zimmerman HM (1962) Alzheimer's neurofibrillary changes: a topographic study. Arch Neurol 7:227–242
Ihara Y, Abraham C, Selkoe DJ (1983) Antibodies to paired helical filaments in Alzheimer's disease do not recognize normal brain proteins. Nature 304:727–730
Ihara Y, Nukina N, Miura R, Ogawara M (1986) Phosphorylated tau protein is integrated into paired helical filaments in Alzheimer's disease. J Biochem 99:1807–1810
Ishino H, Higashi H, Kuroda S, Yabuki S, Hayahara T, Otsuki S (1974) Motor nuclear involvement in progressive supranuclear palsy. J Neurol Sci 22:235–244
Lassmann H, Vass K, Brunner Ch, Seitelberger F (1986) Characterization of inflammatory infiltrates in experimental allergic encephalomyelitis. Prog Neuropathol 6:33–62
Mikol J, Brion S, Guicharnaud L, Waks O (1980) A new case of Pick's disease: anatomical and ultrastructural studies. Acta Neuropathol (Berl) 49:57–61
Nukina N, Ihara Y (1986) One of the antigenic determinants of paired helical filaments is related to tau protein. J Biochem 99:1541–1544
Nukina N, Kosik KS, Selkoe DJ, Ihara Y (1986) Tau protein is integrated into paired helical filaments (PHF) in Alzheimer's disease (AD). J Neuropathol Exp Neurol 45:338 [abstr]
Nukina N, Kosik KS, Selkoe DJ (1987) Recognition of Alzheimer paired helical filaments by monoclonal neurofilament antibodies is due to crossreaction with tau protein. Proc Natl Acad Sci USA 84:3415–3419
Okamoto K, Hirano A, Yamaguchi H, Hirai S (1983) The fine structure of eosinophilic stages of Alzheimer's neurofibrillary tangles. J Clin Electron Microsc 16:77–82
Rudelli R, Welch P, Strom J, Ambler M (1980) Neurofibrillary ultrastructure in post-traumatic premature Alzheimer's disease. J Neuropathol Exp Neurol 39:387 [abstr]
Shibayama H, Kotoh J (1978) Electron microscopic structure of the Alzheimer's neurofibrillary changes in case of atypical senile dementia. Acta Neuropathol (Berl) 41:229–234
Sternberger LA, Sternberger NH (1983) Monoclonal antibodies distinguish phosphorylated and nonphosphorylated forms of neurofilamentsin situ. Proc Natl Acad Sci USA 80:6126–6130
Ulrich J, Haugh M, Anderton BH, Probst A, Lautenschlager C, His B (1987) Alzheimer dementia and Pick's disease: neurofibrillary tangles and Pick bodies are associated with identical phosphorylated neurofilament epitopes. Acta Neuropathol (Berl) 73:240–246
Wisniewski KE, Wisniewski HM, Wen GY (1985) Occurrence of neuropathological changes and dementia of Alzheimer's disease in Down's syndrome. Ann Neurol 17:278–282
Yagishita S, Itoh Y, Nan W, Amano N (1981) Reappraisal of the fine structure of Alzheimer's neurofibrillary tangles. Acta neuropathol (Berl) 54:239–246
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Supported partly by Grant No. 60A-4-20 from the National Center of Neurology and Psychiatry (NCNP) of the Ministry of Health and Welfare of Japan
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Kato, S., Nakamura, H. & Otomo, E. Reappraisal of neurofibrillary tangles. Acta Neuropathol 77, 258–266 (1989). https://doi.org/10.1007/BF00687577
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DOI: https://doi.org/10.1007/BF00687577