Genetic testing in familial and young-onset Alzheimer's disease: mutation spectrum in a Serbian cohort

Abstract Alzheimer's disease (AD) is the most common form of dementia. To date, more than 200 mutations in three genes have been identified as cause of early-onset autosomal dominant inherited AD. The aim of this study was to characterize the mutation spectrum and describe genotype-phenotype correlations in Serbian patients with positive family history of AD or/and early-onset AD. We performed a genetic screening for mutations in the coding regions of Presenilins 1 and 2 ( PSEN1 and PSEN2 ), as well as exons 16 and 17 of the Amyloid Precursor Protein gene ( APP ) in a total of 47 patients from Serbia with a clinical diagnosis of familial and/or early-onset AD (mean age at onset of 60.3 years; range 32–77). We found one novel mutation in PSEN1 , one novel variant in PSEN2 , and three previously described variants, one in each of the analyzed genes. Interestingly, we identified one patient harboring two heterozygous mutations: one in APP (p.L723P) and one in PSEN1 (p.R108Q).