Pharmacogenomics of Alzheimer's disease

Recent advances in genomics and pharmacogenomics pose new challenges for the clinical management of dementia. Alzheimer's disease (AD), as the most frequent form of dementia, is a multifactorial/poligenic complex disorder in which hundreds of different genes are potentially involved, leading to the phenotypic expression of the disease in conjunction with epigenetic and environmental phenomena. Disease-related genomic profiles and genetic variants in genes involved in drug metabolism are responsible for drug efficacy and safety. The field of pharmacogenomics of AD is rapidly expanding and the clinical data of cytochrome c P450 enzymes (CYPs) have been accumulated for clinical application. Interaction of CYP2D6, CYP3A4/5 and AD-related genes will be discussed in this review. To achieve a mature discipline of pharmacogenomics of AD, the following three aspects are proposed: (a) education of physicians and the public on the use of genetic/genomic screening in daily clinical practice; (b) standardization of genetic testing for major categories of drugs; and (c) validation of pharmacogenomic procedures according to drug category and pathology.