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

Area of Science:

• Neuroscience
• Alzheimer's Disease Research
• Animal Models

Background:

• Apathy is a common early symptom in Alzheimer's disease (AD).
• Decreased motor activity in apathy can be monitored using actigraphy.
• The triple transgenic mouse model (3xTgAD) mimics AD biochemical and cognitive changes.

Purpose of the Study:

• To investigate apathy-like behavior in 3xTgAD mice.
• To determine the association between C99 accumulation, synaptic alterations, and apathy.
• To assess the influence of genetic background on these AD-related alterations.

Main Methods:

• Utilized actimetry to measure spontaneous activity in 3xTgAD mice.
• Examined intraneuronal C99 accumulation and synaptic alterations.
• Backcrossed 3xTgAD mice to C57BL/6 to evaluate genetic background effects.

Main Results:

• 3xTgAD mice exhibited early, consistent apathy-like behavior with reduced activity.
• Apathy-like behavior correlated with intraneuronal C99 accumulation and synaptic changes.
• Genetic background did not affect C99 accumulation or synaptic plasticity but significantly influenced apathy-like behavior.

Conclusions:

• Intraneuronal C99 accumulation and synaptic alterations are associated with apathy-like behavior in 3xTgAD mice.
• Genetic background plays a crucial role in modulating apathy-like behavior in this AD model.
• Findings highlight the complexity of AD pathogenesis and the need to consider genetic factors in research.