In addition, the strongest evidence for Aβ42 as the causative molecule for AD is from genetic studies of familial AD (FAD) with mutations in APP, presenilin 1 (PSEN1, PS), or presenilin 2 (PSEN2, PS), which lead to the highest risk for AD among all AD risk genes identified so far [14]. Here, PSEN1 is linked to familial Alzheimer disease.