Journal of Advanced Biomedical Sciences

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Haddadi M. The Most Common Genetic Factors of Alzheimer’s disease and Importance of Fruit Fly in Disease Modeling Studies. JABS 2020; 10 (4) :3085-3096
URL: http://jabs.fums.ac.ir/article-1-2576-en.html

Background & Objective: Alzheimer’s disease (AD) is the major frequent form of dementia in which progressive widespread neuronal death leads to death in affected individuals. AD is a highly heritable disorder and diverse genetic factors contribute to its cause and development. The aim of the present review is to introduce genetic factors involved in AD and to elucidate contributions of Drosophila melanogaster (fruit fly) in the study of mechanisms by which pathogenicity of identified genes occurs. 
Materials & Methods: In this study, 100 published research papers on the genetics of AD and modelling AD in Drosophila melanogaster were investigated. The English articles were retrieved from verified biological databases published from 1992 to 2020.
Result: Based on the presence of clinical symptoms AD is divided into two main types: early-onset AD (EOAD) and late-onset AD (LOAD). The genetic basis for EOAD is mainly related to mutations in genes involved in the production, aggregation, and clearance of amyloid-beta (Aβ). The genetics of LOAD is more complicated and a mixture of common but less-penetrant genetic factors, such as E4 isoform of apolipoprotein E (APOE), interacts with environmental cues and epigenetic influences. Functional studies using fruit flies demonstrate an association between Aß aggregation/clearance and tau phosphorylation. It has been shown that Aß, tau, and APOE4 contribute to damage in axonal terminals in AD conditions.
Conclusion: Knowing the genetic basis of AD and mechanisms that underlie their pathogenicity can be essential for developing effective treatment strategies. Drosophila melanogaster as an ideal model organism with unique genetic characteristics possesses a crucial functional role in the study of the molecular mechanisms of human neurological disorders.