title: Genetic study of familial cases of Alzheimer's disease.
abstract: A small number (1-5%) of Alzheimer's disease (AD) cases associated with the early-onset form of the disease (EOAD) appears to be transmitted as a pure genetic, autosomal dominant trait. To date, three genes responsible for familial EOAD have been identified in the human genome: amyloid precursor protein (APP), presenilin 1 (PS1), and presenilin 2 (PS2). Mutations in these genes account for a significant fraction (18 to 50%) of familial cases of early onset AD. The mutations affect APP processing causing increased production of the toxic Abeta42 peptide. According to the "amyloid cascade hypothesis", aggregation of the Abeta42 peptide in brain is a primary event in AD pathogenesis. In our study of twenty AD patients with a positive family history of dementia, 15% (3 of 20) of the cases could be explained by coding sequence mutations in the PS1 gene. Although a frequency of PS1 mutations is less than 2% in the whole population of AD patients, their detection has a significant diagnostic value for both genetic counseling and treatment in families with AD.
authors.affiliation: Institute of Human Genetics, Polish Academy of Sciences, Poznań, Poland. annkowal@rose.man.poznan.pl
authors.forename: Anna
authors.initials: A
authors.lastname: Kowalska
authors.forename: Danuta
authors.initials: D
authors.lastname: Pruchnik-Wolińska
authors.forename: Jolanta
authors.initials: J
authors.lastname: Florczak
authors.forename: Renata
authors.initials: R
authors.lastname: Modestowicz
authors.forename: Józef
authors.initials: J
authors.lastname: Szczech
authors.forename: Wojciech
authors.initials: W
authors.lastname: Kozubski
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Rossa
authors.forename: Mieczysław
authors.initials: M
authors.lastname: Wender
mesh_terms: D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D001921:Brain / Q000473:pathology / Q000502:physiology*; D003062:Codon / Q000235:genetics; D005091:Exons / Q000235:genetics; D005799:Genes, Dominant; D005817:Genetic Counseling; D015894:Genome, Human; D006801:Humans; D008875:Middle Aged; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide; D053764:Presenilin-1 / Q000737:chemistry / Q000235:genetics*; D053766:Presenilin-2 / Q000235:genetics*; D011487:Protein Conformation
chemical_list: D016564:Amyloid beta-Protein Precursor; D003062:Codon; D053764:Presenilin-1; D053766:Presenilin-2