Early temporal short-term memory deficits in double transgenic APP/PS1 mice

Area of Science:

• Neuroscience
• Genetics
• Pharmacology

Background:

• Alzheimer's disease (AD) is characterized by amyloid pathology.
• Transgenic mouse models are crucial for studying AD pathogenesis and testing therapies.

Purpose of the Study:

• To evaluate the cognitive performance of single and double transgenic mouse models of AD.
• To assess the utility of the differential reinforcement of low rate (DRL) paradigm in detecting early AD-related cognitive deficits.

Main Methods:

• Single APP (Tg2576), PS1 (PS1dE9), and double APP/PS1 transgenic mice were tested at 3 and 6 months of age.
• Cognitive function was assessed using a hippocampal-dependent operant DRL-10s task and a hippocampal-independent signaled DRL-10s (SDRL-10s) task.

Main Results:

• Single APP or PS1 transgenes did not impair DRL-10s learning.
• Double APP/PS1 transgenic mice exhibited deficits in DRL-10s acquisition at 6 months, but not at 3 months.
• APP/PS1 mice showed normal acquisition on the hippocampal-independent SDRL-10s task.

Conclusions:

• The DRL paradigm is sensitive to age-dependent amyloid pathology in APP/PS1 mice.
• APP/PS1 mice represent a valuable model for evaluating therapeutic interventions against Alzheimer's disease.