Conformational change as one of the earliest alterations of tan in Alzheimer's disease

Citation
Cl. Weaver et al., Conformational change as one of the earliest alterations of tan in Alzheimer's disease, NEUROBIOL A, 21(5), 2000, pp. 719-727
Citations number
36
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
NEUROBIOLOGY OF AGING
ISSN journal
0197-4580 → ACNP
Volume
21
Issue
5
Year of publication
2000
Pages
719 - 727
Database
ISI
SICI code
0197-4580(200009/10)21:5<719:CCAOOT>2.0.ZU;2-E
Abstract
Paired helical filaments (PHFs) found in Alzheimer's disease (AD) are mainl y comprised of an abnormal form of tau (PHF-tau) that has undergone several post-translational modifications. Previous studies have shown that the mon oclonal antibody MC1 identifies a distinct conformation of tau in AD. We ha ve assessed the temporal and spatial occurrence of the tau conformation rec ognized by MC1, and found its appearance in hippocampal neurons vulnerable to neurofibrillary tangle (NFT) formation in Braak Stage I and II cases. El ectron 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 immunoblott ing have shown that this material is indistinguishable from that found in N FTs. This soluble component has the ability to self-assemble into PHFs in a concentration-dependent manner. Because the conformational change recogniz ed by MC1 appears before the assembly of and is found in PHF, but is not pr esent in the normal brain, we suggest that the formation of the MC1 epitope is one of the earliest pathological alterations of tau in AD. (C) 2000 Els evier Science Inc. All rights reserved.