Pharmacogenetic considerations in the treatment of Alzheimer's disease.
The practical pharmacogenetics of Alzheimer's disease (AD) is circumscribed to acetylcholinesterase inhibitors (AChEIs) and memantine. However, pharmacogenetic procedures should be applied to novel strategies in AD therapeutics including: novel AChEIs and neurotransmitter regulators, anti-Aβ treatments, anti-tau treatments, pleiotropic products, epigenetic drugs and combination therapies. Genes involved in the pharmacogenetic network are under the influence of the epigenetic machinery which regulates gene expression transcriptionally and post-transcriptionally, configuring the fundamentals of pharmacoepigenomics. Over 60% of AD patients present concomitant pathologies demanding additional treatments which increase the likelihood of drug-drug interactions. Lipid metabolism dysfunction is a pathogenic mechanism inherent to AD neurodegeneration. The therapeutic response to hypolipidemic compounds is influenced by the APOE and CYP genotypes. The development of novel compounds and the use of combination/multifactorial treatments require the implantation of pharmacogenomic procedures for the avoidance of ADRs and the optimization of therapeutics.
Department of Genomic Medicine, Camilo José Cela University, Madrid, Spain.|EuroEspes Biomedical Research Center, Institute of Medical Science and Genomic Medicine, Corunna, Spain.
Ramón
R
Cacabelos
EuroEspes Biomedical Research Center, Institute of Medical Science and Genomic Medicine, Corunna, Spain.
Clara
C
Torrellas
EuroEspes Biomedical Research Center, Institute of Medical Science and Genomic Medicine, Corunna, Spain.
Oscar
O
Teijido
EuroEspes Biomedical Research Center, Institute of Medical Science and Genomic Medicine, Corunna, Spain.
Juan Carlos
JC
Carril
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000235:genetics*; D016229:Amyloid beta-Peptides / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics; D057890:Epigenomics; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics; D010597:Pharmacogenetics / Q000379:methods*; D016875:tau Proteins / Q000235:genetics
D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D016875:tau Proteins
APOE; Alzheimer's disease; CYPs; antidementia drugs; drug interactions; epigenetics; lipid metabolism dysfunction; pharmacoepigenomics; pharmacogenomics; transporters