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 language | English (US) |
|---|---|
| Pages (from-to) | 1496-1504 |
| Number of pages | 9 |
| Journal | Neurobiology of Aging |
| Volume | 36 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 1 2015 |
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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 journal › Article
}
TY - JOUR
T1 - Sustained high levels of neuroprotective, high molecular weight, phosphorylated tau in the longest-lived rodent
AU - Orr, Miranda E.
AU - Garbarino, Valentina R.
AU - Salinas, Angelica
AU - Buffenstein, Rochelle
PY - 2015/3/1
Y1 - 2015/3/1
N2 - 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.
AB - 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.
KW - Aging
KW - Alzheimer's disease
KW - Animal model
KW - Naked mole-rat
KW - Phosphorylation
KW - Tau
UR - http://www.scopus.com/inward/record.url?scp=84923539340&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84923539340&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2014.12.004
DO - 10.1016/j.neurobiolaging.2014.12.004
M3 - Article
C2 - 25576082
AN - SCOPUS:84923539340
VL - 36
SP - 1496
EP - 1504
JO - Neurobiology of Aging
JF - Neurobiology of Aging
SN - 0197-4580
IS - 3
ER -