Opportunities in pharmacogenomics for the treatment of Alzheimer's disease

In Alzheimer's disease (AD), approximately 10-20% of direct costs are associated with pharmacological treatment. Pharmacogenomics account for 30-90% variability in pharmacokinetics and pharmacodynamics. Genes potentially involved in the pharmacogenomics outcome include pathogenic, mechanistic, metabolic, transporter and pleiotropic genes. Over 75% of the Caucasian population is defective for the CYP2D6+ 2C9+ 2C19 cluster. Polymorphic variants in the APOE-TOMM40 region influence AD pharmacogenomics. APOE-4 carriers are the worst responders and APOE-3 carriers are the best responders to conventional treatments. TOMM40 poly T-S/S carriers are the best responders, VL/VL and S/VL carriers are intermediate responders and L/L carriers are the worst responders. The haplotype 4/4-L/L is probably responsible for early onset of the disease, a faster cognitive decline and a poor response to different treatments.