This Article Order Full text via Infotrieve Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ksiezak-Reding, H. Articles by Dickson, D. W. Search for Related Content PubMed PubMed Citation Articles by Ksiezak-Reding, H. Articles by Dickson, D. W.

American Journal of Pathology, Vol 145, 1496-1508, Copyright © 1994 by American Society for Investigative Pathology

REGULAR ARTICLES

Ultrastructure and biochemical composition of paired helical filaments in corticobasal degeneration

H Ksiezak-Reding, K Morgan, LA Mattiace, P Davies, WK Liu, SH Yen, K Weidenheim and DW Dickson
Department of Pathology, Albert Einstein College of Medicine, Bronx, New York 10461.

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.

This article has been cited by other articles:

				D. R. Williams, R. de Silva, D. C. Paviour, A. Pittman, H. C. Watt, L. Kilford, J. L. Holton, T. Revesz, and A. J. Lees Characteristics of two distinct clinical phenotypes in pathologically proven progressive supranuclear palsy: Richardson's syndrome and PSP-parkinsonism Brain, June 1, 2005; 128(6): 1247 - 1258. [Abstract] [Full Text] [PDF]

				W. J. Goux, L. Kopplin, A. D. Nguyen, K. Leak, M. Rutkofsky, V. D. Shanmuganandam, D. Sharma, H. Inouye, and D. A. Kirschner The Formation of Straight and Twisted Filaments from Short Tau Peptides J. Biol. Chem., June 25, 2004; 279(26): 26868 - 26875. [Abstract] [Full Text] [PDF]

				V. Zhukareva, K. Shah, K. Uryu, H. Braak, K. Del Tredici, S. Sundarraj, C. Clark, J. Q. Trojanowski, and V. M.-Y. Lee Biochemical Analysis of {tau} Proteins in Argyrophilic Grain Disease, Alzheimer's Disease, and Pick's Disease : A Comparative Study Am. J. Pathol., October 1, 2002; 161(4): 1135 - 1141. [Abstract] [Full Text] [PDF]

				M. S. Forman, V. Zhukareva, C. Bergeron, S. S.-M. Chin, M. Grossman, C. Clark, V. M.-Y. Lee, and J. Q. Trojanowski Signature Tau Neuropathology in Gray and White Matter of Corticobasal Degeneration Am. J. Pathol., June 1, 2002; 160(6): 2045 - 2053. [Abstract] [Full Text] [PDF]

				M. L. Schmidt, T. Schuck, S. Sheridan, M.-P. Kung, H. Kung, Z.-P. Zhuang, C. Bergeron, J. S. Lamarche, D. Skovronsky, B. I. Giasson, et al. The Fluorescent Congo Red Derivative, (Trans, Trans)-1-Bromo-2,5-Bis-(3-Hydroxycarbonyl-4-Hydroxy)Styrylbenzene (BSB), Labels Diverse {beta}-Pleated Sheet Structures in Postmortem Human Neurodegenerative Disease Brains Am. J. Pathol., September 1, 2001; 159(3): 937 - 943. [Abstract] [Full Text] [PDF]

				G. Hall, B Chu, G Lee, and J Yao Human tau filaments induce microtubule and synapse loss in an in vivo model of neurofibrillary degenerative disease J. Cell Sci., January 4, 2000; 113(8): 1373 - 1387. [Abstract] [PDF]

				M. Goedert and M. Hasegawa The Tauopathies : Toward an Experimental Animal Model Am. J. Pathol., January 1, 1999; 154(1): 1 - 6. [Full Text] [PDF]

				M. G. Spillantini, J. R. Murrell, M. Goedert, M. R. Farlow, A. Klug, and B. Ghetti Mutation in the tau gene in familial multiple system tauopathy with presenile dementia PNAS, June 23, 1998; 95(13): 7737 - 7741. [Abstract] [Full Text] [PDF]

				M. G. Spillantini, M. Goedert, R. A. Crowther, J. R. Murrell, M. R. Farlow, and B. Ghetti Familial multiple system tauopathy with presenile dementia: A disease with abundant neuronal and glial tau filaments PNAS, April 15, 1997; 94(8): 4113 - 4118. [Abstract] [Full Text] [PDF]