A double-labeling immunohistochemical study of tau exon 10 in Alzheimer's disease, progressive supranuclear palsy and Pick's disease

K. Ishizawa, H. Ksiezak-Reding, P. Davies, A. Delacourte, P. Tiseo, S. H. Yen, Dennis W Dickson

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Neurofibrillary tangles (NFT), one of the histopathological hallmarks of Alzheimer's disease (AD) and progressive supranuclear palsy (PSP), and Pick bodies in Pick's disease (PiD) are composed of microtubule-associated protein tau, which is the product of alternative splicing of a gene on chromosome 17. Alternative expression of exon 10 leads to formation of three- or four-repeat tau isoforms. To study the differential expression of exon 10, we performed double-labeling immunohistochemistry of the hippocampal formation in nine AD, four PSP and three PiD cases. Cryostat sections were processed with and without formic acid (FA) treatment, and double-stained with anti-tau (Alz-50 or PHF-1) or anti-amyloid P component antibodies and one of two specific anti-exon 10 antibodies (E-10). The effect of proteinase-K treatment was also evaluated. The results suggest the following. First, in AD, E-10 immunoreactivity is present in most intracellular NFT, but not in most dystrophic neurites and neuropil threads, suggesting differential expression of tau isoforms in specific cellular domains. Second, in AD, E-10 immunoreactivity is lost or blocked in most extracellular NFT, possibly due to proteolysis. Third, in PSP, E-10 immunoreactivity is hidden or blocked in NFT and tau-positive glial inclusions, but FA treatment exposes the epitope consistent with the hypothesis that PSP inclusions contain four-repeat tau. Fourth, E-10 immunoreactivity is present in dentate fascia NFT in AD and PSP but not in Pick bodies in the dentate fascia or other areas. The results suggest that expression of exon 10 in tau is specific for cellular domains in a disease-specific manner.

Original languageEnglish (US)
Pages (from-to)235-244
Number of pages10
JournalActa Neuropathologica
Volume100
Issue number3
StatePublished - Sep 2000

Fingerprint

Pick Disease of the Brain
Progressive Supranuclear Palsy
Neurofibrillary Tangles
formic acid
Exons
Alzheimer Disease
Dentate Gyrus
Protein Isoforms
Neuropil Threads
Serum Amyloid P-Component
Endopeptidase K
Chromosomes, Human, Pair 17
Microtubule-Associated Proteins
Antibodies
Alternative Splicing
Neurites
Neuroglia
Proteolysis
Epitopes
Hippocampus

Keywords

  • Alzheimer's disease
  • Exon 10
  • Pick's disease
  • Progressive supranuclear palsy
  • Tau

ASJC Scopus subject areas

  • Clinical Neurology
  • Pathology and Forensic Medicine
  • Neuroscience(all)

Cite this

A double-labeling immunohistochemical study of tau exon 10 in Alzheimer's disease, progressive supranuclear palsy and Pick's disease. / Ishizawa, K.; Ksiezak-Reding, H.; Davies, P.; Delacourte, A.; Tiseo, P.; Yen, S. H.; Dickson, Dennis W.

In: Acta Neuropathologica, Vol. 100, No. 3, 09.2000, p. 235-244.

Research output: Contribution to journalArticle

Ishizawa, K, Ksiezak-Reding, H, Davies, P, Delacourte, A, Tiseo, P, Yen, SH & Dickson, DW 2000, 'A double-labeling immunohistochemical study of tau exon 10 in Alzheimer's disease, progressive supranuclear palsy and Pick's disease', Acta Neuropathologica, vol. 100, no. 3, pp. 235-244.
Ishizawa K, Ksiezak-Reding H, Davies P, Delacourte A, Tiseo P, Yen SH et al. A double-labeling immunohistochemical study of tau exon 10 in Alzheimer's disease, progressive supranuclear palsy and Pick's disease. Acta Neuropathologica. 2000 Sep;100(3):235-244.
Ishizawa, K. ; Ksiezak-Reding, H. ; Davies, P. ; Delacourte, A. ; Tiseo, P. ; Yen, S. H. ; Dickson, Dennis W. / A double-labeling immunohistochemical study of tau exon 10 in Alzheimer's disease, progressive supranuclear palsy and Pick's disease. In: Acta Neuropathologica. 2000 ; Vol. 100, No. 3. pp. 235-244.
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AU - Delacourte, A.

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AU - Yen, S. H.

AU - Dickson, Dennis W

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