Sporadic Pick's disease: A tauopathy characterized by a spectrum of pathological τ isoforms in gray and white matter
Article first published online: 21 MAY 2002
Copyright © 2002 Wiley-Liss, Inc.
Annals of Neurology
Volume 51, Issue 6, pages 730–739, June 2002
How to Cite
Zhukareva, V., Mann, D., Pickering-Brown, S., Uryu, K., Shuck, T., Shah, K., Grossman, M., Miller, B. L., Hulette, C. M., Feinstein, S. C., Trojanowski, J. Q. and Lee, V. M.-Y. (2002), Sporadic Pick's disease: A tauopathy characterized by a spectrum of pathological τ isoforms in gray and white matter. Ann Neurol., 51: 730–739. doi: 10.1002/ana.10222
- Issue published online: 21 MAY 2002
- Article first published online: 21 MAY 2002
- Manuscript Accepted: 22 FEB 2002
- Manuscript Revised: 20 FEB 2002
- Manuscript Received: 19 DEC 2001
- National Institute on Aging. Grant Numbers: AG17586 (V.M.-Y.L.), AG10124 (J.Q.T.), AG05128 (C.M.H.)
- Oxford Foundation (V.M.-Y.L.)
Pick's disease is characterized neuropathologically by distinct τ-immunoreactive intraneuronal inclusions known as Pick bodies and by insoluble τ proteins with predominantly three microtubule-binding repeat τ isoforms. However, recent immunohistochemical studies showed that the antibody specific for exon 10, which encodes the fourth microtubule-binding repeat, detected other τ lesions in Pick's disease. To better define the spectrum of τ pathology in Pick's disease, we used biochemical, immunohistochemical, and ultrastructural techniques to analyze the τ isoform composition in 14 Pick's disease brains. Western blot analysis showed that both three and four microtubule-binding repeat pathological τ isoforms are present in gray and white matter of various brain regions. Using phosphorylation-dependent anti-τ antibodies, we show that major τ phosphoepitopes are present in sarcosyl-insoluble gray and white matter regions of Pick's disease brains. Also, for the first time to our knowledge, we demonstrated that isoforms with four microtubule-binding repeat τ isoforms are present in Pick bodies from selected brains. Isolated τ filaments were straight or twisted and formed by three microtubule-binding repeat or four microtubule-binding repeat τ isoforms. Major τ phosphorylation–dependent and exon 10–specific epitopes were present in filaments. Therefore, Pick's disease is characterized by an accumulations of Pick bodies in the hippocampal region and cortex as well as the presence of three and four microtubule-binding repeat τ pathology in both cortical gray and white matter that distinguish this tauopathy from other neurodegenerative disorders.