Conformational change as one of the earliest alterations of tau in Alzheimer's disease.
Neurobiol Aging
; 21(5): 719-27, 2000.
Article
en En
| MEDLINE
| ID: mdl-11016541
Paired helical filaments (PHFs) found in Alzheimer's disease (AD) are mainly comprised of an abnormal form of tau (PHF-tau) that has undergone several post-translational modifications. Previous studies have shown that the monoclonal antibody MCI identifies a distinct conformation of tau in AD. We have assessed the temporal and spatial occurrence of the tau conformation recognized by MC1, and found its appearance in hippocampal neurons vulnerable to neurofibrillary tangle (NFT) formation in Braak Stage I and II cases. Electron microscopy has clearly demonstrated that this conformation precedes the formation of PHF. MC1 immunoaffinity chromatography also has identified a nonfilamentous, soluble pool of this abnormal tau. ELISA and immunoblotting have shown that this material is indistinguishable from that found in NFTs. This soluble component has the ability to self-assemble into PHFs in a concentration-dependent manner. Because the conformational change recognized by MCI appears before the assembly of and is found in PHF, but is not present in the normal brain, we suggest that the formation of the MCI epitope is one of the earliest pathological alterations of tau in AD.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Ovillos Neurofibrilares
/
Proteínas tau
/
Enfermedad de Alzheimer
/
Hipocampo
/
Degeneración Nerviosa
Límite:
Aged
/
Aged80
/
Humans
Idioma:
En
Revista:
Neurobiol Aging
Año:
2000
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos