Sustained high levels of neuroprotective, high molecular weight, phosphorylated tau in the longest-lived rodent

Miranda E. Orr, Valentina R. Garbarino, Angelica Salinas, Rochelle Buffenstein

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 Aß accumulation; however, AD animal models, despite elevated Aß, 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 32years), which express appreciable levels of Aß 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 88 kDa, much larger than 45-68kDa tau expressed in other mammals. We propose that this 88 kDa tau protein may offer exceptional microtubule stability and neuroprotection against lifelong, elevated Aß.

Original languageEnglish (US)
Pages (from-to)1496-1504
Number of pages9
JournalNeurobiology of Aging
Volume36
Issue number3
DOIs
StatePublished - Mar 1 2015

Fingerprint

tau Proteins
Rodentia
Alzheimer Disease
Molecular Weight
Phosphorylation
Microtubules
Transgenic Mice
Mammals
Mole Rats
Tauopathies
Axons
Animal Models
Pathology
Brain

Keywords

  • Aging
  • Alzheimer's disease
  • Animal model
  • Naked mole-rat
  • Phosphorylation
  • Tau

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Aging
  • Developmental Biology
  • Geriatrics and Gerontology

Cite this

Sustained high levels of neuroprotective, high molecular weight, phosphorylated tau in the longest-lived rodent. / Orr, Miranda E.; Garbarino, Valentina R.; Salinas, Angelica; Buffenstein, Rochelle.

In: Neurobiology of Aging, Vol. 36, No. 3, 01.03.2015, p. 1496-1504.

Research output: Contribution to journalArticle

Orr, Miranda E. ; Garbarino, Valentina R. ; Salinas, Angelica ; Buffenstein, Rochelle. / Sustained high levels of neuroprotective, high molecular weight, phosphorylated tau in the longest-lived rodent. In: Neurobiology of Aging. 2015 ; Vol. 36, No. 3. pp. 1496-1504.
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