Ultrastructural localization of beta-amyloid, tau, and ubiquitin epitopes in extracellular neurofibrillary tangles
| Autor: | Lucila Autilio-Gambetti, Massimo Tabaton, Valeria Manetto, Giovanni Luigi Mancardi, Sergio Cammarata, P. Gambetti, George Perry |
|---|---|
| Rok vydání: | 1991 |
| Předmět: |
Amyloid
analysis Microtubule-associated protein pathology/ultrastructure Tau protein Immunocytochemistry Nerve Tissue Proteins tau Proteins Hippocampus Epitope Immunoenzyme Techniques Epitopes Alzheimer Disease medicine Extracellular Humans pathology Amyloid beta-Peptides analysis/immunology Epitopes analysis Hippocampus pathology/ultrastructure Humans Immunoenzyme Techniques Microscopy Immunoelectron Microtubule-Associated Proteins analysis/immunology Nerve Tissue Proteins analysis Neurons pathology/ultrastructure Ubiquitins analysis/immunology tau Proteins Microscopy Immunoelectron Ubiquitins Immunoelectron Neurons Microscopy Amyloid beta-Peptides Multidisciplinary biology Chemistry Neurofibrillary tangle medicine.disease analysis/immunology Cell biology Immunology biology.protein pathology Alzheimer's disease Microtubule-Associated Proteins Research Article |
| Zdroj: | Proceedings of the National Academy of Sciences. 88:2098-2102 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.88.6.2098 |
| Popis: | Neurofibrillary tangles (NFTs), a hallmark of Alzheimer disease, are commonly located in perikarya of neurons. In advanced cases of Alzheimer disease, however, NFTs are observed also in the extracellular space. As extracellular NFTs (E-NFTs), and occasionally intracellular NFTs (I-NFTs), are recognized by antibodies to beta-amyloid protein (beta AP), beta AP may be present not only in amyloid deposits but also in paired helical filaments (PHFs), the primary components of NFTs. We compared the antigenic characteristics of I-NFTs and E-NFTs with light- and electron-microscopic immunocytochemistry by using several antibodies to noncontiguous epitopes of the microtubule-associated protein tau and of ubiquitin (Ub) as well as an antiserum to beta AP. At variance with I-NFTs, E-NFTs were made predominantly of straight filaments (SFs), rather than PHFs, that were often separated by astroglial processes and in close association with small beta AP deposits. Occasionally, E-NFTs were made of bundles of amorphous material, which showed no resemblance to SFs, PHFs, or amyloid fibrils. The antigenic changes in E-NFTs suggest that when NFTs become extracellular they lose the N and, possibly, the C termini of tau while maintaining the intermediate region of the molecule; they also lose the N-terminal two-thirds of Ub while the C-terminal conjugation site of Ub is preserved. A small subset of E-NFTs reacted with antibodies to both beta AP and tau. Although in most E-NFTs, the epitopes recognized by tau and Ub antibodies were located in typical PHFs and SFs, the epitopes recognized in this subset of anti-beta AP and anti-tau-positive E-NFTs were located exclusively in the bundles of amorphous material. It is suggested that either beta AP epitopes are present but inaccessible in PHFs and SFs and become exposed after conformational changes occurring in the extracellular space or PHFs and SFs become closely associated with beta AP in the extracellular space. |
| Databáze: | OpenAIRE |
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