Longitudinal behavioral changes in the APP/PS1 transgenic Alzheimer's disease model

Area of Science:

• Neuroscience
• Animal Models
• Alzheimer's Disease Research

Background:

• The APP/PS1 double transgenic mouse model mimics Alzheimer's Disease (AD) pathology.
• Cognitive deficits in AD models require age-related progression analysis.
• Standard water maze assessments offer limited behavioral endpoints.

Purpose of the Study:

• To evaluate longitudinal cognitive and behavioral changes in APP/PS1 mice.
• To assess the impact of repeated testing on water maze performance and AD pathology.
• To determine the utility of comprehensive behavioral assessments in AD mouse models.

Main Methods:

• APP/PS1 transgenic and wildtype mice (n=11/group) were assessed from 7-15 months.
• Behavioral tests included water maze, open field, and motor coordination.
• Body weight and motor coordination were monitored; plaque load was assessed post-mortem.

Main Results:

• APP/PS1 mice showed age-independent hypoactivity in the open field starting at 9 months.
• Water maze deficits (latency, path length) were influenced by thigmotaxis and floating, not solely cognitive impairment.
• Substantial plaque deposition was observed in older transgenic mice, despite stable water maze performance.

Conclusions:

• Longitudinal testing and multiple endpoints are crucial for accurately assessing AD mouse models.
• Repetitive behavioral testing may mitigate cognitive deficits and plaque burden in APP/PS1 mice.
• This study highlights the importance of comprehensive, longitudinal behavioral phenotyping in AD research.