MOLEKULÁRNĚ GENETICKÁ ANALÝZA ALZHEIMEROVYDEMENCE V ČESKÉ POPULACI.Mutace (APP-717) v genu pro amyloidní proteinový prekurzor (APP)

Molecular Genetic Analysis of Alzheimer’s Disease in the Czech Population.Mutation (APP-717) in the Gene for the Amyloid Precursor Protein (APP)

Background.
Although locus mutations in the gene for the amyloid precursor protein were already described inpatients with Alzheimer’s disease, there still are some patients where this mutation was not found and no link wasfound with other possible genetic loci on chromosomes 14 and 19. Therefore a group of subjects with Alzheimer’sdisease was subjected to tests for the presence of a mutation in the APP gene (in position 717).Methods and Results. In a selected group of subjects with Alzheimer’s disease (AD) in the gene for amyloidprecursor protein in position 717 mutations of its transmembraneous region are found. The authors analyzed thegenome DNA of cerebral tissue of Czech subjects for the presence of this mutation by means of the polymerasechain reaction with subsequent verification by sequencing analysis. In every subject genetic analyses from cerebralareas of the frontal lobe, temporal lobe, parietal lobe and hippocampus were performed. The methods used were thepolymerase chain reaction (PCR) and sequencing.From the total number of 18 subjects with confirmed Alzheimer’s disease and six non-related subjects withouthistopathological signs of Alzheimer’s disease after the age of 90 years, three sequencing changes were found inposition 717 of exon 17 of the transmembranous region of the precursor of beta-4 amyloid glycoprotein. In the firstcase it was substitution of thymin for adenine in codon 717, in the second case substitution of cytosine for thymine,in the third case a sporadic mutation of guanine for thymine in codon 717 was found.Conclusions. It was revealed that codon 717 could be a so-called hot spot site preferred for the preferentialdevelopment of mutations in codon 717 in the gene for the amyloid precursor protein (APP).

Key words:
Alzheimer’s disease, amyloid precursor protein, locus mutation, sequencing.