Molecular imaging of NAD + -dependent deacetylase SIRT1 in the brain

Alzheimers Dement. 2021 Dec;17(12):1988-1997. doi: 10.1002/alz.12344. Epub 2021 Apr 15.

Abstract

Introduction: Aging is an inevitable physiological process and the biggest risk factor of Alzheimer's disease (AD). Developing an imaging tracer to visualize aging-related changes in the brain may provide a useful biomarker in elucidating neuroanatomical mechanisms of AD.

Methods: We developed and characterized a new tracer that can be used to visualize SIRT1 in brains related to aging and AD by positron emission tomography imaging.

Results: The SIRT1 tracer displayed desirable brain uptake and selectivity, as well as stable metabolism and proper kinetics and distribution in rodent and nonhuman primate brains. This new tracer was further validated by visualizing SIRT1 in brains of AD transgenic mice, compared to nontransgenic animals.

Discussion: Our SIRT1 tracer not only enables, for the first time, the demonstration of SIRT1 in animal brains, but also allows visualization and recapitulation of AD-related SIRT1 neuropathological changes in animal brains.

Keywords: Alzheimer's disease; SIRT1; molecular imaging; positron emission tomography; preclinical animal models.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism*
  • Alzheimer Disease / pathology*
  • Animals
  • Brain / pathology*
  • Disease Models, Animal
  • Mice
  • Mice, Transgenic
  • Molecular Imaging*
  • NAD / metabolism*
  • Positron-Emission Tomography
  • Sirtuin 1 / metabolism*

Substances

  • NAD
  • Sirtuin 1