Association of the MAOB rs1799836 Single Nucleotide Polymorphism and APOE ɛ4 Allele in Alzheimer's Disease.

BACKGROUND The dopaminergic system is functionally compromised in Alzheimer's dis-ease (AD). The activity of monoamine oxidase B (MAOB), the enzyme involved in the degradation of dopamine, is increased during AD. Also, increased expression of MAOB occurs in the post-mortem hippocampus and neocortex of patients with AD. The MAOB rs1799836 polymorphism modulates MAOB transcription, consequently influencing protein translation and MAOB activity. We recently showed that cerebrospinal fluid levels of amyloid β1-42 are decreased in patients carry- ing the A allele in MAOB rs1799836 polymorphism. OBJECTIVE The present study compares MAOB rs1799836 polymorphism and APOE, the only con- firmed genetic risk factor for sporadic AD. METHOD We included 253 participants, 127 of whom had AD, 57 had mild cognitive impairment, 11 were healthy controls, and 58 suffered from other primary causes of dementia. MAOB and APOE polymorphisms were determined using TaqMan SNP Genotyping Assays. RESULTS We observed that the frequency of APOE ɛ4/ɛ4 homozygotes and APOE ɛ4 carriers is sig- nificantly increased among patients carrying the AA MAOB rs1799836 genotype. CONCLUSION These results indicate that the MAOB rs1799836 polymorphism is a potential genetic biomarker of AD and a potential target for the treatment of decreased dopaminergic transmission and cognitive deterioration in AD.