Butyrylcholinesterase-knockout reduces fibrillar β-amyloid and conserves 18FDG retention in 5XFAD mouse model of Alzheimer's disease

Brain Res. 2017 Sep 15:1671:102-110. doi: 10.1016/j.brainres.2017.07.009. Epub 2017 Jul 17.


Alzheimer's disease (AD) is the most common neurodegenerative disorder causing dementia. One hallmark of the AD brain is the deposition of β-amyloid (Aβ) plaques. AD is also a state of cholinergic dysfunction and butyrylcholinesterase (BChE) associates with Aβ pathology. A transgenic mouse (5XFAD) is an aggressive amyloidosis model, producing Aβ plaques with which BChE also associates. A derived strain (5XFAD/BChE-KO), with the BChE gene knocked out, has significantly lower fibrillar Aβ than 5XFAD mice at the same age. Therefore, BChE may have a role in Aβ pathogenesis. Furthermore, in AD, diminished glucose metabolism in the brain can be detected in vivo with positron emission tomography (PET) imaging following 2-deoxy-2-(18F)fluoro-D-glucose (18FDG) administration. To determine whether hypometabolism is related to BChE-induced changes in fibrillar Aβ burden, whole brain and regional uptake of 18FDG in 5XFAD and 5XFAD/BChE-KO mice was compared to corresponding wild-type (WT5XFAD and WTBChE-KO) strains at 5months. Diminished fibrillar Aβ burden was confirmed in 5XFAD/BChE-KO mice relative to 5XFAD. 5XFAD and 5XFAD/BChE-KO mice demonstrated reduction in whole brain 18FDG retention compared to respective wild-types. Regional analysis of relevant AD structures revealed reduction in 18FDG retention in 5XFAD mice in all brain regions analyzed (save cerebellum) compared to WT5XFAD. Alternatively, 5XFAD/BChE-KO mice demonstrated a more selective pattern of reduced retention in the cerebral cortex and thalamus compared to WTBChE-KO, while retention in hippocampal formation, amygdala and basal ganglia remained unchanged. This suggests that in knocking out BChE and reducing fibrillar Aβ, a possible protective effect on brain function may be conferred in a number of structures in 5XFAD/BChE-KO mice.

Keywords: (18)FDG; 5XFAD mouse; Alzheimer’s disease; Butyrylcholinesterase (BChE); Positron emission tomography (PET); β-Amyloid.

MeSH terms

  • Alzheimer Disease / diagnostic imaging
  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism*
  • Amyloid / genetics
  • Amyloid / metabolism*
  • Amyloid beta-Peptides / genetics
  • Amyloid beta-Peptides / metabolism*
  • Amyloid beta-Protein Precursor / genetics
  • Amyloid beta-Protein Precursor / metabolism
  • Animals
  • Basal Ganglia / metabolism
  • Brain / metabolism
  • Butyrylcholinesterase / deficiency*
  • Butyrylcholinesterase / genetics
  • Butyrylcholinesterase / metabolism
  • Disease Models, Animal
  • Female
  • Fluorodeoxyglucose F18 / pharmacology*
  • Gene Knockout Techniques
  • Glucose / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Plaque, Amyloid / metabolism
  • Positron-Emission Tomography / methods
  • Radiopharmaceuticals / pharmacokinetics


  • Amyloid
  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Radiopharmaceuticals
  • Fluorodeoxyglucose F18
  • Butyrylcholinesterase
  • Glucose