To understand the effects of the UNC5C T835M mutation on AD pathogenesis, we generated mice that were homozygous for both UNC5C T835M and the APP targeted replacement, AppNL−G−F/NL−G−F (NLGF) [16], which develop amyloid plaques and synaptic loss by 6 months but no significant neuron loss. Here, UNC5C is linked to Alzheimer disease.