Genetic study of familial cases of Alzheimer's disease.
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.
Kowalska
Anna
A
Institute of Human Genetics, Polish Academy of Sciences, Poznań, Poland. annkowal@rose.man.poznan.pl
Pruchnik-Wolińska
Danuta
D
Florczak
Jolanta
J
Modestowicz
Renata
R
Szczech
Józef
J
Kozubski
Wojciech
W
Rossa
Grzegorz
G
Wender
Mieczysław
M
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
D016564:Amyloid beta-Protein Precursor; D003062:Codon; D053764:Presenilin-1; D053766:Presenilin-2