Amyloid-β Increases Tau by Mediating Sirtuin 3 in Alzheimer’s Disease

Junxiang Yin, Pengcheng Han, Melissa Song, Megan Nielsen, Thomas G. Beach, Geidy E. Serrano, Winnie S. Liang, Richard J. Caselli, Jiong Shi

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Increasing evidence indicates that sirtuin 3 (Sirt3) has neuroprotective effects in regulating oxidative stress and energy metabolism, both of which are involved in the pathogenesis of Alzheimer’s disease (AD). However, it is unclear whether Sirt3 is associated with cognitive performance and pathological changes in AD. We conducted a case-control study of the postmortem brains of AD (n = 16), mild cognitive impairment (n = 13), and age- and education-matched cognitively normal (CN, n = 11) subjects. We measured the mRNA and protein levels of Sirt3 and assessed their association with cognitive performance and AD pathology. In an ex vivo model of cortical neurons from transgenic mice that carry human tau protein, we modified Sirt3 expression by genetic knockdown and knock-in to investigate the cause-effect relationship between Sirt3 and tau. Sirt3 levels were reduced in the entorhinal cortex, the middle temporal gyrus, and the superior frontal gyrus of AD subjects compared to those of CN. This reduction was associated with poorer test scores of neuropsychological evaluation and the severity of tau pathology. Further study with genetic manipulation of Sirt3 revealed that amyloid-β increased levels of total tau acetylated tau through its modulation of Sirt3. These data suggest that reduction of Sirt3 is critically involved in pathogenesis of AD.

Original languageEnglish (US)
Pages (from-to)8592-8601
Number of pages10
JournalMolecular Neurobiology
Volume55
Issue number11
DOIs
StatePublished - Nov 1 2018

Keywords

  • Acetylation
  • Alzheimer’s disease
  • Amyloid
  • Mild cognitive impairment
  • Sirtuin
  • Tau

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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  • Cite this

    Yin, J., Han, P., Song, M., Nielsen, M., Beach, T. G., Serrano, G. E., Liang, W. S., Caselli, R. J., & Shi, J. (2018). Amyloid-β Increases Tau by Mediating Sirtuin 3 in Alzheimer’s Disease. Molecular Neurobiology, 55(11), 8592-8601. https://doi.org/10.1007/s12035-018-0977-0