Relationship between , , and Genetic Variants and Neuropsychiatric Symptoms in Patients with Alzheimer's Disease.

Alzheimer's disease (AD) is characterized by the presence of neuropsychiatric or behavioral and psychological symptoms of dementia (BPSD). BPSD have been associated with the allele, which is also the major genetic AD risk factor. Although the involvement of some circadian genes and orexin receptors in sleep and behavioral disorders has been studied in some psychiatric pathologies, including AD, there are no studies considering gene-gene interactions. The associations of one variant in , two in , two in and two in were evaluated in 31 AD patients and 31 cognitively healthy subjects. Genotyping was performed using real-time PCR and capillary electrophoresis from blood samples. The allelic-genotypic frequencies of variants were calculated for the sample study. We explored associations between allelic variants with BPSD in AD patients based on the NPI, PHQ-9 and sleeping disorders questionnaires. Our results showed that the allele is an AD risk variant ( = 0.03). The remaining genetic variants did not reveal significant differences between patients and controls. The _rs228697 variant showed a nine-fold increased risk for circadian rhythm sleep-wake disorders in Mexican AD patients, and our gene-gene interaction analysis identified a novel interaction between and gene variants. These findings need to be further confirmed in larger samples.