Levels of soluble and insoluble tau reflect overall status of tau phosphorylation in vivo
| Autor: | Paul S. Aisen, Yasuji Matsuoka, Chiho Hirata-Fukae, Li Ma, G. William Rebeck, Hui Fang Li, Hyang-Sook Hoe |
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| Rok vydání: | 2008 |
| Předmět: |
Genetically modified mouse
Male Aging Guanylate kinase Transgene Synaptophysin Hyperphosphorylation Mice Transgenic tau Proteins Receptors N-Methyl-D-Aspartate Mice In vivo Alzheimer Disease mental disorders medicine Animals Receptors AMPA Phosphorylation Receptor Neurons Analysis of Variance Chemistry General Neuroscience Intracellular Signaling Peptides and Proteins Brain Membrane Proteins medicine.disease Disease Models Animal Biochemistry Solubility Tauopathy Disks Large Homolog 4 Protein Guanylate Kinases |
| Zdroj: | Neuroscience letters. 450(1) |
| ISSN: | 0304-3940 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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