Sulfo-glycosaminoglycan content affects PHF-tau solubility and allows the identification of different types of PHFs.
Sulfo-glycosaminoglycans (sGAGs) are involved in the assembly of tau in at least a subpopulation of paired helical filaments (PHFs) in Alzheimer's disease (AD). To further understand the role of sGAG molecules in the structure of PHFs, we isolated PHFs from patients with AD and treated them with heparinase. Immunoelectron microscopy and Western blotting (WB) were used later on to analyze the changes obtained. The heparinase treatment abolished Tau14 and AT8 immunodecoration (two N-terminal tau antibodies) and increased PHF-1 labeling (a C-terminal antibody). In addition, heparinase-treated filaments are more labile than control ones as demonstrated by sodium dodecyl sulfate-extraction and subsequent WB. In summary, our results demonstrate that sGAG content affects PHF conformation as well as PHF-tau solubilization.
Hernández
Félix
F
Severo Ochoa Center for Molecular Biology, CSIC/UAM, Faculty of Sciences, Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain.
Pérez
Mar
M
Lucas
José J
JJ
Avila
Jesús
J
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D000595:Amino Acid Sequence / Q000502:physiology; D000906:Antibodies; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D006025:Glycosaminoglycans / Q000737:chemistry*; D019763:Heparin Lyase; D006801:Humans; D007150:Immunohistochemistry; D008854:Microscopy, Electron; D008968:Molecular Conformation; D016874:Neurofibrillary Tangles / Q000737:chemistry* / Q000648:ultrastructure; D009474:Neurons / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D020033:Protein Isoforms / Q000737:chemistry / Q000648:ultrastructure; D017434:Protein Structure, Tertiary / Q000187:drug effects / Q000502:physiology; D012995:Solubility; D013463:Sulfuric Acid Esters / Q000737:chemistry*; D016875:tau Proteins / Q000737:chemistry* / Q000648:ultrastructure
D000906:Antibodies; D000939:Epitopes; D006025:Glycosaminoglycans; D020033:Protein Isoforms; D013463:Sulfuric Acid Esters; D016875:tau Proteins; D019763:Heparin Lyase