Cloning of Presenilin 2 cDNA and Construction of Vectors Carrying Effective Mutations in the Pathogenesis of Familial Alzheimer's Disease

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease and is identified by the detection of amyloid-plaques and neurofibrillary tangles in the brain. Amyloid precursor protein gene, presenilin 1 (PSEN1) gene, and presenilin 2 (PSEN2) gene are responsible for this disease. PSEN2 and amyloid precursor protein (APP) gene mutations are a much rarer cause of familial AD patients. This study aims to clone the PSEN2 gene and create vectors with different mutations by directed mutagenesis. As a result of the experiments, the PSEN2 cDNA was cloned between the BamHI and KpnI cut-off points of the pBluescript II sk (+) vector. PSEN1 and PSEN2 homologs have a role in cell destiny decision and AD progress. We studied some of the PSEN2 mutations (Ala252Thr and Pro334Arg) and provided expression analysis in eukaryotic cell cultures. Amyloid beta-protein (A beta), which is produced by endoproteolytic cleavage of the APP, is considered to play a role in AD. While nominal concentration of A beta 40 is 10 times of A beta 42 , the last peptide is firmly linked to AD pathogenesis. Amyloid (beta-protein is generated by the gamma-secretase cleavage of APP onset and the progression of AD, and it is the primary ingredient of the senile plaques. The A beta 42 dodecamer plays a central role in AD. In future studies, it will be determined if there is an increase in A beta 42 protein levels, and the effect on this early onset AD can be identified.