The double‐immunostaining of the brain section from AD O‐tau injected mice with T22 and AT8 antibodies showed that only large aggregates were both T22 and AT8 positive, while the small aggregates stained with T22 but not with AT8 (Figure 5D), supporting that during tau pathogenesis, T22 pathological change may precede AT8 pathological change.46 This evidence concerns the gene MAPT and Alzheimer disease.