Effects of APOE, ACE, PICALM, and CYP2D6 Gene Variants on Alzheimer's Disease

Abstract

Background: Alzheimer’s disease is a multifactorial, neurodegenerative disease which is considered the most common cause of dementia. It is divided into two subtypes based on the age of onset: Early-Onset Alzheimer’s Disease (EOAD) and Late-Onset Alzheimer’s Disease (LOAD). Objective: In this study, we aimed to analyse the polymorphisms of APOE2/E3/E4, ACE I/D, PICALM rs3851179, which are thought to increase the risk of disease, and CYP2D6 rs1080985, that affects the therapy response. Methods: 102 early onset and 99 late onset Alzheimer's patients diagnosed according to DSM-IV and NINCDS-ADRDA diagnostic criteria were included in the study. MMSE test was applied at the time of diagnosis and the control examination was performed after 6 months. We analysed the polymorphisms of APOE2/E3/E4 by fragment analysis and ACE I/D, PICALM rs3851179, CYP2D6 rs1080985 by Real Time- PCR. The response of the therapy and effects on prognosis were compared between groups by Mini-Mental State Exam test scores. Results: The score differences of the women were significantly lower than men’s score differences. The score differences of the EOAD group were significantly lower than the LOAD group in women. Family history situation was higher in men compared to women. The score differences were higher at CC genotype for PICALM rs3851179 in the EOAD group; the score differences were higher at E3/E4 genotype than E2/E2 genotype in LOAD. Also, the score differences were significantly higher at PICALM rs3851179 in the acetylcholinesterase inhibitor+antidepressant therapy group. Conclusions: The relationship between the treatment groups and related gene regions was investigated extensively for the first time in the literature. As a result, it will be a guide in the clinic in light of the findings of the prognosis and pharmacogenetic interactions of the disease obtained from the study.