A Conformation- and Phosphorylation-Dependent Antibody Recognizing the Paired Helical Filaments of Alzheimer's Disease
Article first published online: 18 NOV 2002
Journal of Neurochemistry
Volume 69, Issue 5, pages 2087–2095, November 1997
How to Cite
Jicha, G. A., Lane, E., Vincent, I., Otvos, L., Hoffmann, R. and Davies, P. (1997), A Conformation- and Phosphorylation-Dependent Antibody Recognizing the Paired Helical Filaments of Alzheimer's Disease. Journal of Neurochemistry, 69: 2087–2095. doi: 10.1046/j.1471-4159.1997.69052087.x
- Issue published online: 18 NOV 2002
- Article first published online: 18 NOV 2002
- Received June 2, 1997; revised manuscript received June 30, 1997; accepted June 30, 1997.
- Alzheimer's disease;
- Paired helical filaments;
Abstract: Hyperphosphorylated tau (PHF-tau) is the major constituent of paired helical filaments (PHFs) from Alzheimer's disease (AD) brains. This conclusion has been based largely on the creation and characterization of monoclonal antibodies raised against PHFs, which can be classified in three categories: (a) those recognizing unmodified primary sequences of tau, (b) those recognizing phosphorylation-dependent epitopes on tau, and (c) those recognizing conformation-dependent epitopes on tau. Recent studies have suggested that the antibodies recognizing primary sequence and phosphorylation-dependent epitopes on tau are unable to distinguish between normal adult biopsy tau and PHF-tau. We now present evidence for a new fourth class of monoclonal antibodies recognizing conformation-dependent phosphoepitopes on tau, typified by TG-3, a monoclonal antibody raised to PHFs from AD brain homogenates. Studies using a series of deletional tau mutants, site-directed tau mutants, and synthetic peptides enable the precise epitope mapping of TG-3. Additional studies demonstrate that TG-3 reacts with neonatal mouse tau and PHF-tau but does not recognize adult mouse tau or tau derived from normal human autopsy or biopsy tissue. Further investigation reveals that TG-3 recognizes a unique conformation of tau found almost exclusively in PHFs from AD brains.