In the present study, we (a) determined the timing of amyloid‐β appearance over age, (b) tested a hypothesis that human AD‐relevant age‐associated events (i.e., neuroinflammation, misregulations in proteins involved in oxidative stress, mitochondrial energy metabolism, or β‐oxidation/peroxisome) are associated with amyloid‐β accumulation in the Sgo1−/+ model, and (c) identified the GSK3‐ARC/Arg3.1 and GSK3‐Wnt signaling axes as candidates for triggering amyloid‐β accumulation in middle age. Here, ARC is linked to Alzheimer disease.