PICALM and Alzheimer disease: Genes that accumulate pathogenic variants more frequently in the same patient with AD are PRNP, PSEN1, ACE, A2M, BIN1, CLU, CPZ, LHFPL6, MS4A6A, MS4A4E, and PICALM. Over 80% of AD patients in the Caucasian population are deficient metabolizers for the most common drugs, which are metabolized via CYP2D6, CYP2C9, CYP2C19, and CYP3A4/5 enzymes.