Levels of soluble and insoluble tau reflect overall status of tau phosphorylation in vivo
Copyright policy )Levels of soluble and insoluble tau reflect overall status of tau phosphorylation in vivo
The clinical progression of Alzheimer's disease is closely related to tau pathology. Hyperphosphorylation of tau precedes histopathological evidence of tangle formation, and modulation of tau phosphorylation is a promising therapeutic target. Although some phosphorylation sites are more critical in pathological processes, the importance of each phosphorylation site is unclear. In this study, we found that levels of phosphorylated tau drastically increased in crude and insoluble tau fractions with aging in a transgenic mouse model of Alzheimer-type tauopathy. However, changes in the soluble tau fraction were minor and phosphorylation at some sites was even reduced with aging. Total soluble (presumably functional) tau was reduced, while insoluble tau increased with aging. Synaptic proteins were reduced as insoluble tau increased. Taken together, these findings suggest that levels of soluble and insoluble tau are indicative of overall levels of tau phosphorylation, and may be useful markers to evaluate the effects of anti-tau therapeutic strategies in vivo.
- University of California, San Diego United States
- University of California, San Diego United States
- University of Washington Medical Center United States
- Georgetown University Medical Center United States
Male, Neurons, Aging, Analysis of Variance, Intracellular Signaling Peptides and Proteins, Synaptophysin, Brain, Membrane Proteins, Mice, Transgenic, tau Proteins, Receptors, N-Methyl-D-Aspartate, Disease Models, Animal, Mice, Solubility, Alzheimer Disease, Animals, Receptors, AMPA, Phosphorylation, Disks Large Homolog 4 Protein, Guanylate Kinases
Male, Neurons, Aging, Analysis of Variance, Intracellular Signaling Peptides and Proteins, Synaptophysin, Brain, Membrane Proteins, Mice, Transgenic, tau Proteins, Receptors, N-Methyl-D-Aspartate, Disease Models, Animal, Mice, Solubility, Alzheimer Disease, Animals, Receptors, AMPA, Phosphorylation, Disks Large Homolog 4 Protein, Guanylate Kinases
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).14 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Average impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!