Title

Tau-66: evidence for a novel tau conformation in Alzheimer's disease

Document Type

Article

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, Abeta(1-40), or Abeta(1-42), 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.

Medical Subject Headings

Aged; Aged, 80 and over; Alzheimer Disease (genetics, metabolism); Antibodies, Monoclonal (chemistry, immunology); Antibody Specificity; Blotting, Western; Enzyme-Linked Immunosorbent Assay; Epitopes; Female; Fluorescent Antibody Technique, Indirect; Humans; Hybridomas; Immunohistochemistry; Male; Microscopy, Confocal; Middle Aged; Neurofibrillary Tangles (metabolism, pathology); Protein Conformation; tau Proteins (chemistry, immunology)

Publication Date

6-1-2001

Publication Title

Journal of neurochemistry

ISSN

0022-3042

Volume

77

Issue

5

First Page

1372

Last Page

85

PubMed ID

11389188

Digital Object Identifier (DOI)

10.1046/j.1471-4159.2001.00346.x

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