Influence of Genetic Background on Apathy-Like Behavior in Triple Transgenic AD Mice

Curr Alzheimer Res. 2016;13(8):942-9. doi: 10.2174/1567205013666160404120106.


Apathy is an early and common neuropsychiatric syndrome in Alzheimer's disease (AD) patients. In clinical trials, apathy is associated with decreased motor activity that can be monitored by actigraphy. The triple transgenic mouse AD model (3xTgAD) has been shown to recapitulate the biochemical lesions as well as many of the synaptic and cognitive alterations associated with AD. In the present work we found that these mice also develop an early and consistent apathy-like behavior as evidenced by a drastic decrease in spontaneous activity measured by actimetry. We recently established that these mice also display an intraneuronal accumulation of the β-secretase-derived βAPP fragment (C99) appearing early, in absence of Aβ. Interestingly, we found that the apathy-like behavior observed in 3xTgAD mice was temporally associated with C99 accumulation and synaptic alterations. Since it is well known that the genetic background can strongly influence behavior and can induce transcriptional variability in animal models, we decided to determine the influence of genetic background on the above-described alterations. We backcrossed 3xTgAD mice to C57BL/6 and found that the genetic background had no influence on either C99 accumulation or synaptic plasticity alterations, but strongly affected the apathy-like behavior.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / genetics
  • Aging / metabolism
  • Aging / pathology
  • Aging / psychology
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Alzheimer Disease / psychology*
  • Amyloid beta-Protein Precursor / genetics
  • Amyloid beta-Protein Precursor / metabolism
  • Animals
  • Apathy*
  • CA1 Region, Hippocampal / metabolism
  • CA1 Region, Hippocampal / pathology
  • Circadian Rhythm / genetics
  • Circadian Rhythm / physiology
  • Disease Models, Animal
  • Genetic Background
  • Humans
  • Long-Term Potentiation / genetics
  • Long-Term Potentiation / physiology
  • Male
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Mice, Transgenic / genetics*
  • Motor Activity / genetics*
  • Motor Activity / physiology
  • Species Specificity
  • Synapses / metabolism
  • Synapses / pathology
  • tau Proteins / genetics
  • tau Proteins / metabolism


  • APP protein, human
  • Amyloid beta-Protein Precursor
  • MAPT protein, human
  • tau Proteins