Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6804662 | Neurobiology of Aging | 2015 | 9 Pages |
Abstract
Tau protein is primarily expressed in neuronal axons and modulates microtubule stability. Tau phosphorylation, aggregation, and subcellular mislocalization coincide with neurodegeneration in numerous diseases, including Alzheimer's disease (AD). During AD pathogenesis, tau misprocessing accompanies AÃ accumulation; however, AD animal models, despite elevated AÃ, fail to develop tauopathy. To assess whether lack of tau pathology is linked to short life span common to most AD models, we examined tau processing in extraordinarily long-lived, mouse-sized naked mole-rats (NMRs; approximately 32Â years), which express appreciable levels of AÃ throughout life. We found that NMRs, like other mammals, display highest tau phosphorylation during brain development. Although tau phosphorylation decreases with aging, unexpectedly adult NMRs have higher levels than transgenic mice overexpressing mutant human tau. However, in sharp contrast with the somatodendritic accumulation of misprocessed tau in the transgenic mice, NMRs maintain axonal tau localization. Intriguingly, the adult NMR tau protein is 88Â kDa, much larger than 45-68Â kDa tau expressed in other mammals. We propose that this 88Â kDa tau protein may offer exceptional microtubule stability and neuroprotection against lifelong, elevated AÃ.
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Authors
Miranda E. Orr, Valentina R. Garbarino, Angelica Salinas, Rochelle Buffenstein,