Behavioral Testing for Memory and Cognition
Objective: To assess memory loss and cognitive deficits in transgenic mice expressing mutant amyloid precursor proteins (APP), specifically examining the relationship between amyloid-beta aggregates and memory impairment in Tg2576 mice
Protocol Steps
Parallel Study Design Setup
Study two lines of APP transgenic mice expressing comparable levels of mutant and wild-type human APP in parallel to distinguish between age-dependent and age-independent behavioral changes
Note: This parallel design enabled identification of age-independent behavioral deficits not specifically related to mutant APP expression
View evidence from paper
“we studied in parallel two lines of APP transgenic mice expressing comparable levels of mutant and wild-type human APP”
Behavioral Testing for Memory Loss
Conduct behavioral testing to detect memory loss in transgenic mice expressing mutant APP (Tg2576 mice)
Note: Memory loss detection coincided with the appearance of detergent-insoluble Aβ aggregates
View evidence from paper
“we detected memory loss in transgenic mice expressing mutant APP (Tg2576 mice) starting at ∼6 months, which coincided with the appearance of detergent-insoluble Aβ aggregates”
Age Stratification Analysis
Stratify mice by age and analyze correlations between memory performance and Aβ insoluble aggregates in both young and old mice
Note: Inverse correlations between memory and Aβ insoluble aggregates became evident when mice were stratified by age
View evidence from paper
“when the mice were stratified by age, whereupon inverse correlations between memory and Aβ insol became evident”
Extended Analysis with Genetically Accelerated Mice
Include mice with genetically accelerated formation of Aβ insoluble aggregates to examine earlier onset of memory decline
Note: Genetically accelerating the formation of Aβ insoluble resulted in an earlier onset of memory decline
View evidence from paper
“Genetically accelerating the formation of Aβ insol resulted in an earlier onset of memory decline”