Background information: 5xFAD (Familiar Alzheimer Disease) mice bear 5 mutations, 3 in the APP695 gene [APP K670N/M671L (Swedish), I716V (Florida), V717I (London)] as well as 2 mutations in the presenilin 1 gene [PS1 M146L, L286V] (Oakley et al., 2006). The expression of the 5xFAD transgene is driven by the neuron-specific Thy1 promoter. 5xFAD mice recapitulate many AD-related phenotypes and have a relatively early and aggressive disease presentation.

Animals: Male/Female 5xFAD mice {hemizygous for the APP and PSEN1 transgenes in the B6SJLF1 hybrid (C57BL/6J and SJL/J) background}.

Efficacy test: Test articles are administered in a medicalized diet for 4-5 months (starting at 2-months old) and efficacy is assessed at specified time points.

Assessments: Body weight & Food Consumption (weekly), T-maze (1 mo), Voluntary Wheel Running (2.5 mo) & Morris Water Maze (Spatial learning, Retention memory and Flexibility learning, 4 mo).& Biomarkers (at the end of treatment).

Positive control: Sigma-2 receptor antagonist.

Criteria for significance: ANOVA followed by Dunnett’s test is applied for comparison between the vehicle and treatment groups. Significant activity is considered at the P<0.05 level.

Turnaround time: 10 months (behavioral studies).