Tau-66: Evidence for a novel tau conformation in alzheimer's disease

Nupur Ghoshal, Francisco García-Sierra, Yifan Fu, Laurel A Beckett, Elliott J. Mufson, Jeff Kuret, Robert W. Berry, Lester I. Binder

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

We have characterized a novel monoclonal antibody, Tau-66, raised against recombinant human tau. Immunohistochemistry using Tau-66 reveals a somatic-neuronal stain in the superior temporal gyrus (STG) that is more intense in Alzheimer's disease (AD) brain than in normal brain. In hippocampus, Tau-66 yields a pattern similar to STG, except that neurofibrillary lesions are preferentially stained if present. In mild AD cases, Tau-66 stains plaques lacking obvious dystrophic neurites (termed herein 'diffuse reticulated plaques') in STG and the hippocampus. Enzyme-linked immunosorbent assay (ELISA) analysis reveals that Tau-66 is specific for tau, as there is no cross-reactivity with MAP2, tubulin, Aβ1-40, or Aβ1-42, although Tau-66 fails to react with tau or any other polypeptide on western blots. The epitope of Tau-66, as assessed by ELISA testing of tau deletion mutants, appears discontinuous, requiring residues 155-244 and 305-314. Tau-66 reactivity exhibits buffer and temperature sensitivity in an ELISA format and is readily abolished by SDS treatment. Taken together these lines of evidence indicate that the Tau-66 epitope is conformation-dependent, perhaps involving a close interaction of the proline-rich and the third microtubule-binding regions. This is the first indication that tau can undergo this novel folding event and that this conformation of tau is involved in AD pathology.

Original languageEnglish (US)
Pages (from-to)1372-1385
Number of pages14
JournalJournal of Neurochemistry
Volume77
Issue number5
DOIs
StatePublished - 2001
Externally publishedYes

Fingerprint

Conformations
Alzheimer Disease
Immunosorbents
Temporal Lobe
Assays
Enzyme-Linked Immunosorbent Assay
Epitopes
Brain
Coloring Agents
Enzymes
Tau-66
Parahippocampal Gyrus
Pathology
Neurites
Tubulin
Proline
Microtubules
Hippocampus
Buffers
Western Blotting

Keywords

  • Alzheimer's disease
  • Antibody
  • Conformation
  • Epitope
  • Tau

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Ghoshal, N., García-Sierra, F., Fu, Y., Beckett, L. A., Mufson, E. J., Kuret, J., ... Binder, L. I. (2001). Tau-66: Evidence for a novel tau conformation in alzheimer's disease. Journal of Neurochemistry, 77(5), 1372-1385. https://doi.org/10.1046/j.1471-4159.2001.00346.x

Tau-66 : Evidence for a novel tau conformation in alzheimer's disease. / Ghoshal, Nupur; García-Sierra, Francisco; Fu, Yifan; Beckett, Laurel A; Mufson, Elliott J.; Kuret, Jeff; Berry, Robert W.; Binder, Lester I.

In: Journal of Neurochemistry, Vol. 77, No. 5, 2001, p. 1372-1385.

Research output: Contribution to journalArticle

Ghoshal, N, García-Sierra, F, Fu, Y, Beckett, LA, Mufson, EJ, Kuret, J, Berry, RW & Binder, LI 2001, 'Tau-66: Evidence for a novel tau conformation in alzheimer's disease', Journal of Neurochemistry, vol. 77, no. 5, pp. 1372-1385. https://doi.org/10.1046/j.1471-4159.2001.00346.x
Ghoshal, Nupur ; García-Sierra, Francisco ; Fu, Yifan ; Beckett, Laurel A ; Mufson, Elliott J. ; Kuret, Jeff ; Berry, Robert W. ; Binder, Lester I. / Tau-66 : Evidence for a novel tau conformation in alzheimer's disease. In: Journal of Neurochemistry. 2001 ; Vol. 77, No. 5. pp. 1372-1385.
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