Alzheimer's Disease (AD) is a progressive neurodegenerative disease and pathologically characterized by the presence of neurofibrillary tangles (tau aggregation) and amyloid plaques (amyloid-beta (A!) aggregation). PSEN1 protein with 9 transmembrane helices acts as aspartyl protease and is one of the catalytic components of γ secretase complex, that cleaves amyloid precursor protein (APP). Furthermore, PSEN1 protein plays a significant role in the process of APP and in the generation of amyloid

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... beta (Aβ). In the present study, it was aimed to estimate the probable deleterious effects of missense SNPs in PSEN1 gene that is associated with AD on protein stability and structure by using bioinformatics tools. SIFT, PolyPhen-2, PROVEAN, PhD-SNP, and PANTHER PSEP software were used to estimate the deleterious SNPs, whereas I-Mutant 3.0 and MUpro web tools were used to determine the effects of amino acid substitution on protein stability. Additionally, the effects of wild type and mutant amino acids on protein threedimensional structure via modeling were predicted by Project HOPE webserver. The phylogenetic conservation of amino acid residues of PSEN1 protein was analyzed by ConSurf. In total, 386 missense SNPs were found in the human PSEN1 gene from the National Center for Biotechnology Information Single Nucleotide Polymorphism (NCBI dbSNP) database and 65 SNPs of which