Different tau epitopes define Abeta42-mediated tau insolubility.
Alzheimer's disease (AD) is characterized by extracellular beta-amyloid (Abeta(42))-containing plaques and intracellular neurofibrillary tangles. The latter are composed of hyperphosphorylated filamentous aggregates of the microtubule-associated protein tau. Previously we demonstrated pathological interactions between these two histopathological hallmarks using human SH-SY5Y neuroblastoma cells overexpressing wild-type and mutant forms of human tau. Exposure to pre-aggregated forms of Abeta(42) caused both the formation of AD-like tau-containing filaments and a decreased solubility of tau, both of which were prevented by mutating the S422 phospho-epitope of tau. Here, we expressed additional tau mutants in SH-SY5Y cells to assess the role of phosphorylation and cleavage sites of tau in tau aggregation. We found that the Abeta(42)-mediated decrease in tau solubility depends on the interplay of distinct phospho-epitopes of tau and not only on phosphorylation of the S422 epitope.
Pennanen
Luis
L
Division of Psychiatry Research, University of Zürich, August Forel Street 1, 8008 Zürich, Switzerland.
Götz
Jürgen
J
D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D001921:Brain / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D000939:Epitopes / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D012995:Solubility; D016875:tau Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D000939:Epitopes; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins