Differential activation of the mTOR/autophagy pathway predicts cognitive performance in APP/PS1 mice

Neurobiol Aging. 2019 Nov:83:105-113. doi: 10.1016/j.neurobiolaging.2019.08.018. Epub 2019 Sep 3.

Abstract

The molecular bases underlying cognitive impairments in Alzheimer's disease remain elusive. In this study, we sought to determine the molecular correlates of memory deficits in APP/PS1 mice, a widely used animal model of Alzheimer's disease. To this end, we tested 18-month-old APP/PS1 mice in the Morris water maze and ranked them by their spatial memory performance. We found that some APP/PS1 mice performed poorly, whereas others performed as well as nontransgenic mice. We took advantage of this intragroup variability to identify the best predictor of cognitive deficits. In this APP/PS1 cohort, soluble and insoluble amyloid-β levels did not correlate significantly with cognitive performance. However, we found that cognitive performance within the APP/PS1 group had a strong inverse correlation with Aβ plaque load and mammalian target of rapamycin activation and positively correlated with autophagy activation. Our data suggest that mammalian target of rapamycin signaling may account cognitive performance in APP/PS1 mice.

Keywords: AD; Alzheimer's disease; Aβ; Plaques; Tangles; tau.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alzheimer Disease / metabolism
  • Alzheimer Disease / physiopathology*
  • Amyloid beta-Peptides / metabolism
  • Amyloid beta-Protein Precursor / metabolism
  • Animals
  • Autophagy / physiology*
  • Cognitive Dysfunction / metabolism*
  • Cognitive Dysfunction / physiopathology
  • Disease Models, Animal
  • Hippocampus / metabolism
  • Memory Disorders / metabolism
  • Memory Disorders / physiopathology
  • Mice, Transgenic
  • Plaque, Amyloid / metabolism*
  • Spatial Memory / physiology

Substances

  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor