Abstract
ABSTRACT
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.
Papers of special note have been highlighted as: • of interest; •• of considerable interest
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doi:10.3233/JAD-142841 (2015) (Epub ahead of print).