This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Services Related articles in Am J Pathol 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 Forman, M. S. Articles by Trojanowski, J. Q. Search for Related Content PubMed PubMed Citation Articles by Forman, M. S. Articles by Trojanowski, J. Q.

(American Journal of Pathology. 2002;160:2045-2053.)
© 2002 American Society for Investigative Pathology

Regular Articles

Signature Tau Neuropathology in Gray and White Matter of Corticobasal Degeneration

Mark S. Forman^*, Victoria Zhukareva^*, Catherine Bergeron, Steven S.-M. Chin, Murray Grossman^¶, Chris Clark^¶, Virginia M.-Y. Lee^* and John Q. Trojanowski^*

From the Center for Neurodegenerative Disease Research^*and the Departments of Pathology and Laboratory Medicineand Neurology,^¶University of Pennsylvania, Philadelphia, Pennsylvania; the Center for Research in Neurodegenerative Diseases and the Department of Laboratory Medicine and Pathobiology,University of Toronto, Toronto, Canada; and the Department of Pathology,Columbia University College of Physicians and Surgeons, New York, New York

Corticobasal degeneration (CBD) is an adult-onset progressive neurodegenerative disorder characterized by L-dopa-resistant rigidity, focal cortical deficits, and variable dementia. The neuropathological hallmark of CBD is the deposition of filamentous inclusions in neurons and glia composed of hyperphosphorylated tau with only four microtubule-binding repeats (4R-tau). To characterize the regional burden of tau pathology in CBD, we studied 12 brains with the neuropathological diagnosis of CBD using biochemical and histochemical techniques. Eleven brain regions were evaluated including gray and white matter from frontal, parietal, temporal, and occipital lobes and cerebellum as well as basal ganglia. Although the distribution of tau pathology was variable, neuropathological and biochemical data showed a similar burden of tau abnormalities in frontal, temporal, and parietal lobes and basal ganglia of both hemispheres. This included abundant, sarkosyl-insoluble 4R-tau in both gray and white matter of two or more of these cortical regions and basal ganglia, and to a lesser extent, cerebellar white matter. The insoluble tau pathology in gray and white matter showed overlapping but distinct phosphorylated epitopes suggesting cell-type and subcellular localization (ie, cell bodies versus cell processes)-specific differences in tau phosphorylation. In contrast, soluble tau was composed of normal 4R/3R-tau ratios indicating no gross abnormality in tau splicing. Thus, although clinically heterogeneous, CBD is a distinct lobar and basal ganglionic tauopathy with selective aggregation of 4R-tau.

Related articles in Am J Pathol:

This Month in AJP

Am J Pathol 2002 160: 1915-1916. [Full Text]  

This article has been cited by other articles:

				J. M. Anderson, D. W. Hampton, R. Patani, G. Pryce, R. A. Crowther, R. Reynolds, R. J. M. Franklin, G. Giovannoni, D. A. S. Compston, D. Baker, et al. Abnormally phosphorylated tau is associated with neuronal and axonal loss in experimental autoimmune encephalomyelitis and multiple sclerosis Brain, July 1, 2008; 131(7): 1736 - 1748. [Abstract] [Full Text] [PDF]

				B. Borroni, V. Garibotto, C. Agosti, S. M. Brambati, G. Bellelli, R. Gasparotti, A. Padovani, and D. Perani White Matter Changes in Corticobasal Degeneration Syndrome and Correlation With Limb Apraxia Arch Neurol, June 1, 2008; 65(6): 796 - 801. [Abstract] [Full Text] [PDF]

				E J Kim, G D Rabinovici, W W Seeley, C Halabi, H Shu, M W Weiner, S J DeArmond, J Q Trojanowski, M L Gorno-Tempini, B L Miller, et al. Patterns of MRI atrophy in tau positive and ubiquitin positive frontotemporal lobar degeneration J. Neurol. Neurosurg. Psychiatry, December 1, 2007; 78(12): 1375 - 1378. [Abstract] [Full Text] [PDF]

				I. Vulih-Shultzman, A. Pinhasov, S. Mandel, N. Grigoriadis, O. Touloumi, Z. Pittel, and I. Gozes Activity-Dependent Neuroprotective Protein Snippet NAP Reduces Tau Hyperphosphorylation and Enhances Learning in a Novel Transgenic Mouse Model J. Pharmacol. Exp. Ther., November 1, 2007; 323(2): 438 - 449. [Abstract] [Full Text] [PDF]

				M. Grossman, D. J. Libon, M. S. Forman, L. Massimo, E. Wood, P. Moore, C. Anderson, J. Farmer, A. Chatterjee, C. M. Clark, et al. Distinct Antemortem Profiles in Patients With Pathologically Defined Frontotemporal Dementia Arch Neurol, November 1, 2007; 64(11): 1601 - 1609. [Abstract] [Full Text] [PDF]

				R. Murray, M. Neumann, M. S. Forman, J. Farmer, L. Massimo, A. Rice, B. L. Miller, J. K. Johnson, C. M. Clark, H. I. Hurtig, et al. Cognitive and motor assessment in autopsy-proven corticobasal degeneration Neurology, April 17, 2007; 68(16): 1274 - 1283. [Abstract] [Full Text] [PDF]

				D. J. Libon, S. X. Xie, P. Moore, J. Farmer, S. Antani, G. McCawley, K. Cross, and M. Grossman Patterns of neuropsychological impairment in frontotemporal dementia Neurology, January 30, 2007; 68(5): 369 - 375. [Abstract] [Full Text] [PDF]

				M. Higuchi, B. Zhang, M. S. Forman, Y. Yoshiyama, J. Q. Trojanowski, and V. M.-Y. Lee Axonal Degeneration Induced by Targeted Expression of Mutant Human Tau in Oligodendrocytes of Transgenic Mice That Model Glial Tauopathies J. Neurosci., October 12, 2005; 25(41): 9434 - 9443. [Abstract] [Full Text] [PDF]

				C. H. Halpern, G. Glosser, R. Clark, J. Gee, P. Moore, K. Dennis, C. McMillan, A. Colcher, and M. Grossman Dissociation of numbers and objects in corticobasal degeneration and semantic dementia Neurology, April 13, 2004; 62(7): 1163 - 1169. [Abstract] [Full Text] [PDF]

				V. Zhukareva, J. Q. Trojanowski, and V. M.-Y. Lee Assessment of Pathological Tau Proteins in Frontotemporal Dementias: Qualitative and Quantitative Approaches Am J Geriatr Psychiatry, April 1, 2004; 12(2): 136 - 145. [Abstract] [Full Text] [PDF]

				M. Grossman, C. McMillan, P. Moore, L. Ding, G. Glosser, M. Work, and J. Gee What's in a name: voxel-based morphometric analyses of MRI and naming difficulty in Alzheimer's disease, frontotemporal dementia and corticobasal degeneration Brain, March 1, 2004; 127(3): 628 - 649. [Abstract] [Full Text] [PDF]

				D. V. Dabir, J. Q. Trojanowski, C. Richter-Landsberg, V. M.-Y. Lee, and M. S. Forman Expression of the Small Heat-Shock Protein {alpha}B-Crystallin in Tauopathies with Glial Pathology Am. J. Pathol., January 1, 2004; 164(1): 155 - 166. [Abstract] [Full Text] [PDF]

				Y. Yoshiyama, B. Zhang, J. Bruce, J. Q. Trojanowski, and V. M.-Y. Lee Reduction of Detyrosinated Microtubules and Golgi Fragmentation Are Linked to Tau-Induced Degeneration in Astrocytes J. Neurosci., November 19, 2003; 23(33): 10662 - 10671. [Abstract] [Full Text] [PDF]

				O. Goldbaum, M. Oppermann, M. Handschuh, D. Dabir, B. Zhang, M. S. Forman, J. Q. Trojanowski, V. M.-Y. Lee, and C. Richter-Landsberg Proteasome Inhibition Stabilizes Tau Inclusions in Oligodendroglial Cells that Occur after Treatment with Okadaic Acid J. Neurosci., October 1, 2003; 23(26): 8872 - 8880. [Abstract] [Full Text] [PDF]

				J.R. Hodges, R. Davies, J. Xuereb, J. Kril, and G. Halliday Survival in frontotemporal dementia Neurology, August 12, 2003; 61(3): 349 - 354. [Abstract] [Full Text] [PDF]