Age and gender differences for the behavioral phenotypes of 3xTg alzheimer's disease mice

Brain Res. 2021 Jul 1;1762:147437. doi: 10.1016/j.brainres.2021.147437. Epub 2021 Mar 19.


The triple transgenic Alzheimer's disease (3xTg-AD) strain is a common mouse model used for studying the pathology and mechanism of Alzheimer's disease (AD). The 3xTg-AD strain exhibits two hallmarks of AD, amyloid beta (Aβ) and neurofibrillary tangles. Several studies using different gender and age of 3xTg-AD mice to investigate their behavior phenotypes under the influence of various treatments have reported mixed results. Therefore, a comprehensive investigation on the optimal gender, age, and training paradigms used for behavioral studies of 3xTg-AD is necessary. In the present study, we investigated the behavioral phenotypes for the two genders of 3xTg-AD mice at 3, 6, 9, and 12 months old and compared the results with age-, gender-matched C57BL/6N control strain. All mice were subjected to tail flick, pinprick, open field, elevated plus maze, passive avoidance, and trace fear conditioning (TFC) tests to evaluate their sensory, locomotor, anxiety, and learning/memory functions. The results showed that TFC on male 3xTg-AD mice is optimal for studying the memory performance in AD. The sensory and locomotor functions of 3xTg-AD mice for two genders appear to be normal before 6 months, decline in fear memory afterwards. The differences between control and 3xTg-AD male mice in contextual and cued memory are robust, thus they are ideal for evaluating the effect of a treatment. Since it is costly and time consuming to obtain wildtype littermates as controls, C57BL/6N strain is suggested to be used as control mice because their baseline performance of sensorimotor functions are similar to that of 3xTg-AD mice.

Keywords: 3xTg-AD; Alzheimer’s disease; Elevated plus maze; Learning and memory; Passive avoidance; Trace fear conditioning (TFC).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / psychology
  • Animals
  • Avoidance Learning / physiology*
  • Fear / physiology*
  • Fear / psychology
  • Female
  • Locomotion / physiology
  • Male
  • Maze Learning / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Phenotype*
  • Sex Characteristics*