Screening targeted DNA gene variations in sporadic alzheimer's disease

Alzheimer's disease (AD) is a multifactorial complex neurodegenerative disorder and it is the most frequent type of dementia. By discovering that, an early diagnosis slows down the progression of sporadic AD and reducing its symptoms, research studies about genetic risk factors of sporadic AD has been accelerated. The relationship between base excision repair (BER) damages and AD etiology and pathology has come to light by biochemical, molecular, cellular and behavioral researches on post-mortem brain tissues of sporadic Alzheimer patients, mouse models, cell lines and also knockout mouse models for specific BER genes. Research studies have shown that, in sporadic AD, BER protein POL β expression, activity and amount is at low levels and total BER capacity has decreased depending on low levels of POL β. Therefore during this research post-mortem brain tissues from AD patients has scanned for POL β gene locus with next-generation sequencing. Rs3136797 (pro242arg) polymorphism located in exon 12 of POL β gene and 63 intronic polymorphisms have been detected. Among the genetic variatons found in this study, some of the polymorphisms detected only in Alzheiemer patients and are discovered for the first time with this study and their frequency in the population is not known. Polymorphisms related with other than AD and with minor allele frequency (maf) lower than 1% has been shown in Alzheimer patients for the first time in this study. Although there is no significantly dominating polymorphism in majority of the AD patients, more than one POL β gene polymorphism has found in one patient which can cause an additive effect. To find out whether these polymorphisms could be considered as a biomarker for sporadic AD, sample numbers should be increased with population studies, frequency of the variants which are considered to be important in the population should be investigated and compared with the frequency in sporadic AD patients. The roles of newly discovered genetic variant on AD etiology should be studied functionally in future researches.