Department of Public Health Sciences

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

Ghoshal, N, F Garcia-Sierra, Y Fu, L A Beckett, E J Mufson, J Kuret, R W Berry and L I Binder

J Neurochem. 2001. 77(5):1372-85.

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.

Keywords: 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, Human, Hybridomas, Immunohistochemistry, Male, Microscopy, Confocal, Middle Age, Neurofibrillary Tangles/metabolism/pathology, Protein Conformation, Support, U.S. Gov't, P.H.S., tau Proteins/chemistry/*immunology



Close Window

UC Davis Health System is pleased to provide this information for general reference purposes only. It should not be considered as a substitute for professional medical advice. You are urged to consult with your health care provider for diagnosis of and treatment for any health-related condition. The information provided herein may not and should not be used for diagnosis and treatment.

Reproduction of material on this web site is hereby granted solely for personal use. No other use of this material is authorized without prior written approval of UC Regents.