title: Molecular genetics of Alzheimer's disease: presenilin 1 gene analysis in a cohort of patients from the Poznań region.
abstract: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by memory loss and personality changes. Pathological hallmarks of AD are: deposition of amyloid plaques and neurofibrillary tangles in the brain, accompanied by neuronal and synaptic loss. The genetic background of AD is heterogeneous and strongly depends on the form of the disease. In most of the families with early-onset AD (EOAD) (10% of the total population of patients), the disease segregates as an autosomal dominant fully penetrant trait. To date, some missense mutations in three genes encoding the amyloid precursor protein, presenilin 1 (PS1) and 2 (PS2) have been found to cause familial EOAD. We screened for mutations in the presenilin genes in a sample of 55 patients with familial or sporadic form of EOAD from the Poznan region. We found 4 missense mutations in the PS1 gene: A246E in exon 7, P267L in exon 8, E318G in exon 9, and L424R in exon 12 among 5 unrelated patients. The frequency of PS1 mutations was 11% (5 of 55) in the whole sample of the patients with EOAD or 50% (3 of 6) if the analysis was restricted to familial cases with a positive history of dementia in the patient's family.
authors.affiliation: Institute of Human Genetics, Polish Academy of Sciences, ul. Strzeszyńska 32, 60-479 Poznań. annkowal@rose.man.poznan.pl
authors.forename: Anna
authors.initials: A
authors.lastname: Kowalska
authors.forename: Mieczyslaw
authors.initials: M
authors.lastname: Wender
authors.forename: Jolanta
authors.initials: J
authors.lastname: Florczak
authors.forename: Danuta
authors.initials: D
authors.lastname: Pruchnik-Wolinska
authors.forename: Renata
authors.initials: R
authors.lastname: Modestowicz
authors.forename: Józef
authors.initials: J
authors.lastname: Szczech
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Rossa
authors.forename: Wojciech
authors.initials: W
authors.lastname: Kozubski
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D008957:Models, Genetic; D009154:Mutation; D020125:Mutation, Missense; D011044:Poland; D053764:Presenilin-1; D013997:Time Factors
chemical_list: D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1