The Pathogenic Component of the APOE-TOMM40 Region in Alzheimer's disease: Its Implications in Metabolomics and Pharmacogenomics

The genetic and epigenetic defects identified so far in Alzheimer's disease (AD) include Mendelian mutations, susceptibility singlenucleotide polymorphisms, mitochondrial DNA (mtDNA) mutations, and epigenetic changes. Mendelian mutations affect genes directly linked to AD, including mutations in the amyloid beta precursor protein gene (21q21) (AD1), mutations in the presenilin 1 (PSEN1 ) gene (14q24.3) (AD3 ), and mutations in the presenilin 2 (PSEN2 ) gene (1q31-q42) (AD4) [1-2]. There are over 600 genes potentially associated with AD, of which the top ten are APOE (19q13.2), BIN1 (2q14), CLU (8p21-p12), ABCA7 (19p13.3), CR1 (1q32), PICALM (11q14), MS4A6A (11q12.1), CD33 (19q13.3), MS4A4E (11q12.2), and CD2AP (6p12). In a recent study [58], the structure of the APOE-TOMM40 region has been investigated in Spanish patients with dementia, as well as the influence of polymorphic variants in this genomic segment on the therapeutic response to a multifactorial treatment adapted to the pathogenic profile of the patients.