Ultrastructure and biochemical composition of paired helical filaments in corticobasal degeneration

Hanna Ksiezak-Reding, Karen Morgan, Linda A. Mattiace, Peter Davies, Wan Kyng Liu, Shu Hui Yen, Karen M. Weidenheim, Dennis W. Dickson

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Abstract

Corticobasal degeneration (CBD) is a neurodegenerative disorder associated with extensive cytoskeletal abnormalities. These include tau-positive neuropil threads and grains, ballooned or swollen neurons, neurofibrillary tangles, and glial inclusions. Given the presence of tau-positive structures in CBD, we investigated whether abnormalities in tau proteins associated with CBD were similar to those in Alzheimer's disease (AD). Fractions of abnormal tau proteins were isolated as Sarkosyl-insoluble pellets. By electron microscopic examination, the fraction from CBD contained twisted filaments that differed from paired helical filaments of AD. In CBD, filaments were shorter in length, rarely longer than 400 nm, 10 to 20% wider in the maximum and minimum widths (26 to 28 nm and 13 to 14 nm, respectively), and the periodic twist (169 to 202 nm) was twice as long as that in AD. Immunogold labeling with a panel of tau-reactive antibodies (Alz 50, Tau 14, AH-1, E- 11, PHF-1, and Tau 46) showed no apparent differences in the pattern of tau immunoreactivity between filaments of CBD and AD. Western blots revealed that polypeptides of abnormal tau were present in both fractions; however, only two polypeptides (68 and 64 kd) were present in CBD as compared with three (68, 64, and 60 kd) in AD. Both of these polypeptides were reactive with additional antibodies (E-9, Tau-1 after dephosphorylation, AT8, and NP8). Only one polypeptide (68 kd) bound an antibody to adult-specific tau sequence encoded by exon 2, but neither was reactive with antibodies to adult-specific sequences encoded by exons 3 and 10. The results suggest that abnormalities in the number and heterogeneity of isoforms of tau may be one of the factors contributing to ultrastructural differences in pathological filaments of CBD and AD.

Original languageEnglish (US)
Pages (from-to)1496-1508
Number of pages13
JournalAmerican Journal of Pathology
Volume145
Issue number6
StatePublished - Dec 1994

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Alzheimer Disease
tau Proteins
Peptides
Antibodies
Exons
Neuropil Threads
Neurofibrillary Tangles
Neuroglia
Neurodegenerative Diseases
Protein Isoforms
Western Blotting
Electrons
Neurons
tau-1 monoclonal antibody

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Ksiezak-Reding, H., Morgan, K., Mattiace, L. A., Davies, P., Liu, W. K., Yen, S. H., ... Dickson, D. W. (1994). Ultrastructure and biochemical composition of paired helical filaments in corticobasal degeneration. American Journal of Pathology, 145(6), 1496-1508.

Ultrastructure and biochemical composition of paired helical filaments in corticobasal degeneration. / Ksiezak-Reding, Hanna; Morgan, Karen; Mattiace, Linda A.; Davies, Peter; Liu, Wan Kyng; Yen, Shu Hui; Weidenheim, Karen M.; Dickson, Dennis W.

In: American Journal of Pathology, Vol. 145, No. 6, 12.1994, p. 1496-1508.

Research output: Contribution to journalArticle

Ksiezak-Reding, H, Morgan, K, Mattiace, LA, Davies, P, Liu, WK, Yen, SH, Weidenheim, KM & Dickson, DW 1994, 'Ultrastructure and biochemical composition of paired helical filaments in corticobasal degeneration', American Journal of Pathology, vol. 145, no. 6, pp. 1496-1508.
Ksiezak-Reding H, Morgan K, Mattiace LA, Davies P, Liu WK, Yen SH et al. Ultrastructure and biochemical composition of paired helical filaments in corticobasal degeneration. American Journal of Pathology. 1994 Dec;145(6):1496-1508.
Ksiezak-Reding, Hanna ; Morgan, Karen ; Mattiace, Linda A. ; Davies, Peter ; Liu, Wan Kyng ; Yen, Shu Hui ; Weidenheim, Karen M. ; Dickson, Dennis W. / Ultrastructure and biochemical composition of paired helical filaments in corticobasal degeneration. In: American Journal of Pathology. 1994 ; Vol. 145, No. 6. pp. 1496-1508.
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abstract = "Corticobasal degeneration (CBD) is a neurodegenerative disorder associated with extensive cytoskeletal abnormalities. These include tau-positive neuropil threads and grains, ballooned or swollen neurons, neurofibrillary tangles, and glial inclusions. Given the presence of tau-positive structures in CBD, we investigated whether abnormalities in tau proteins associated with CBD were similar to those in Alzheimer's disease (AD). Fractions of abnormal tau proteins were isolated as Sarkosyl-insoluble pellets. By electron microscopic examination, the fraction from CBD contained twisted filaments that differed from paired helical filaments of AD. In CBD, filaments were shorter in length, rarely longer than 400 nm, 10 to 20{\%} wider in the maximum and minimum widths (26 to 28 nm and 13 to 14 nm, respectively), and the periodic twist (169 to 202 nm) was twice as long as that in AD. Immunogold labeling with a panel of tau-reactive antibodies (Alz 50, Tau 14, AH-1, E- 11, PHF-1, and Tau 46) showed no apparent differences in the pattern of tau immunoreactivity between filaments of CBD and AD. Western blots revealed that polypeptides of abnormal tau were present in both fractions; however, only two polypeptides (68 and 64 kd) were present in CBD as compared with three (68, 64, and 60 kd) in AD. Both of these polypeptides were reactive with additional antibodies (E-9, Tau-1 after dephosphorylation, AT8, and NP8). Only one polypeptide (68 kd) bound an antibody to adult-specific tau sequence encoded by exon 2, but neither was reactive with antibodies to adult-specific sequences encoded by exons 3 and 10. The results suggest that abnormalities in the number and heterogeneity of isoforms of tau may be one of the factors contributing to ultrastructural differences in pathological filaments of CBD and AD.",
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AU - Liu, Wan Kyng

AU - Yen, Shu Hui

AU - Weidenheim, Karen M.

AU - Dickson, Dennis W.

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AB - Corticobasal degeneration (CBD) is a neurodegenerative disorder associated with extensive cytoskeletal abnormalities. These include tau-positive neuropil threads and grains, ballooned or swollen neurons, neurofibrillary tangles, and glial inclusions. Given the presence of tau-positive structures in CBD, we investigated whether abnormalities in tau proteins associated with CBD were similar to those in Alzheimer's disease (AD). Fractions of abnormal tau proteins were isolated as Sarkosyl-insoluble pellets. By electron microscopic examination, the fraction from CBD contained twisted filaments that differed from paired helical filaments of AD. In CBD, filaments were shorter in length, rarely longer than 400 nm, 10 to 20% wider in the maximum and minimum widths (26 to 28 nm and 13 to 14 nm, respectively), and the periodic twist (169 to 202 nm) was twice as long as that in AD. Immunogold labeling with a panel of tau-reactive antibodies (Alz 50, Tau 14, AH-1, E- 11, PHF-1, and Tau 46) showed no apparent differences in the pattern of tau immunoreactivity between filaments of CBD and AD. Western blots revealed that polypeptides of abnormal tau were present in both fractions; however, only two polypeptides (68 and 64 kd) were present in CBD as compared with three (68, 64, and 60 kd) in AD. Both of these polypeptides were reactive with additional antibodies (E-9, Tau-1 after dephosphorylation, AT8, and NP8). Only one polypeptide (68 kd) bound an antibody to adult-specific tau sequence encoded by exon 2, but neither was reactive with antibodies to adult-specific sequences encoded by exons 3 and 10. The results suggest that abnormalities in the number and heterogeneity of isoforms of tau may be one of the factors contributing to ultrastructural differences in pathological filaments of CBD and AD.

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