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- Title
Conformational changes and truncation of tau protein during tangle evolution in Alzheimer's disease.
- Authors
García-Sierra, Francisco; Ghoshal, Nupur; Quinn, Bruce; Berry, Robert W.; Binder, Lester I.
- Abstract
The conformation-dependent antibodies Tau-66 and Alz-50 recognize discontinuous epitopes on the tau molecule (residues 155–244 & 305–314 and 5–15 & 312–322, respectively), thereby defining two distinct conformations. In double- and triple-label immunofluorescence experiments we discovered that specific populations of neurofibrillary tangles display either the Alz-50 or the Tau-66 conformation, but not both. In combination with other antibodies to several domains of the molecule we demonstrate that the conformation recognized by Alz-50 seems to be an early event in the formation of neurofibrillary tangles. This conformation is characterized by the presence of predominantly intact N- and C- termini. By contrast, the Tau-66 conformation is likely a later event in tangle development, being favored in structures containing truncations of both the N- and C- termini. We propose a sequence of events that occurs during the formation and evolution of neurofibrillary tangles based on the initial conformation adopted by tau. In this scheme, the Tau-66 conformation in neurofibrillary tangles may arise from amino and carboxy truncation of tau after it has assumed the Alz-50 conformation. These results indicate that tau structure within the NFT is dynamic in that tau can undergo a "refolding" event following N- and C-terminal truncation.
- Subjects
PROTEINS; ALZHEIMER'S disease; IMMUNOGLOBULINS; MOLECULES
- Publication
Journal of Alzheimer's Disease, 2003, Vol 5, Issue 2, p65
- ISSN
1387-2877
- Publication type
Article
- DOI
10.3233/JAD-2003-5201