PIK3R1 and Alzheimer disease: Activated phosphoinositide 3-kinase delta syndrome (APDS) is caused by autosomal dominant (AD) gain-of-function (GoF) mutations in PIK3CD (APDS1), AD loss-of-function (LoF) mutations in PIK3R1 (APDS2) or PTEN (phosphatase and tensin homolog deleted on chromosome 10).