Modeling this prolonged silent phase of asymptomatic amyloidosis has been challenging as standard Aβ/APP transgenic overexpression models consistently develop dementia-like deficits before the onset of Aβ pathology31,32—likely due to supraphysiological Aβ/APP expression—a disease stage never observed in either sporadic or in familial AD, where amyloidosis precedes cognitive decline. This evidence concerns the gene APP and dementia.