In many ways, the above hypothesis has been highly successful, in that it unites findings from many different investigative approaches to the disease and, most compellingly, helps to explain how mutations in genes APP, presenilin 1 (PSEN1), or PSEN2 can cause the familial early-onset form of AD, which accounts for ~5% of all cases [4–5]. Here, PSEN1 is linked to Alzheimer disease.