Prevalence of APP-associated novel polymorphism in Pakistani Population

Abstract

Alzheimer’s disease is a prevalent neurodegenerative disease characterized by dementia occurs in aged individuals. The report of prevalence of AD showed that AD and dementia patients are estimated as 35.6 million in 2010 and this number can reach up to 66 million by 2030. The present study is the first one to assess the presence of APP genotype in the Pakistani population with relevance to AD, and structural analysis of wild type APP, 710 (V>G) and 718 (I>L), and 720 (L>S) mutated APP with ligands (BACE1, ADAM10, and Nicastrin). No study of this sort has been carried out in Pakistan before. The in silico results showed that mutated APP at 718 codon interacts with serine residue of BACE1, and tyrosine residue with Nicastrin. Change in these residues cause protein to undergo aberrant denaturing and results in generation of amyloids due to differential binding of mutated APP protein with ligands in AD. SNP analysis showed the prevalence of 718 (I>L) mutation in 4% of studied population. Symptoms of 718 (I>L), mutation in APP are Hippocampus atrophy, dementia with remarkable oral tendency, and Amnesia. It is imperative to establish organizations that can create awareness among the masses regarding AD which is exponentially increasing in Pakistan.