Tau-66: evidence for a novel tau conformation in Alzheimer's disease
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)
Journal of neurochemistry
Digital Object Identifier (DOI)
Ghoshal, N; García-Sierra, F; Fu, Y; Beckett, L A.; Mufson, E J.; Kuret, J; Berry, R W.; and Binder, L I., "Tau-66: evidence for a novel tau conformation in Alzheimer's disease" (2001). Translational Neuroscience. 1969.