Among the elegant proposals [214] and elaborated suggestions [213] formulated to provide a working framework to elucidate the etiopathogenic processes in sAD, we put forward a reductionist approach for furthering research into the development of novel AD therapies based on the notion that IGF-I activity in the brain may serve as a biomarker of resilience/vulnerability to AD pathology. Here, IGF1 is linked to Alzheimer disease.