title: The APP A673T frequency differs between Nordic countries.
abstract: A coding gene variant A673T (rs63750847) in the APP gene has recently been recognized as a protective variant of late-onset Alzheimer's Disease in a large Icelandic population and has been observed recurrently in populations from Nordic countries. The variant also was related to longevity in the Icelandic population. However, because of the extreme rarity of A673T in non-Nordic populations, the association with Alzheimer's disease has not yet been formally replicated. Because the variant has not been reported among the Danes, we aimed to study its frequency among healthy middle-age twins and oldest-old singletons and explore the possible effects on longevity and cognitive abilities. Surprisingly, only 1 of 3487 unrelated Danes carried the A673T variant, (0.014% [95% CI 0.000-0.080]), which was significantly lower than in the other Nordic countries averaging to 0.43% (95% CI 0.40-0.46). In conclusion, the A673T variant is rarer in Danes than other Nordic countries, thus precluding assessment of association with longevity or cognitive functioning.
authors.affiliation: The Danish Aging Research Center and The Danish Twin Registry, Epidemiology, Biostatistics and Biodemography Unit, Department of Public Health, University of Southern Denmark, Odense, Denmark; Department of Clinical Genetics, Odense University Hospital, Odense, Denmark. Electronic address: jmengel-from@health.sdu.dk.
authors.forename: Jonas
authors.initials: J
authors.lastname: Mengel-From
authors.affiliation: The Danish Aging Research Center and The Danish Twin Registry, Epidemiology, Biostatistics and Biodemography Unit, Department of Public Health, University of Southern Denmark, Odense, Denmark.
authors.forename: Bernard
authors.initials: B
authors.lastname: Jeune
authors.affiliation: Research Program Unit, Molecular Neurology, Biomedicum-Helsinki, University of Helsinki, Helsinki, Finland; Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Tienari
authors.initials: T
authors.lastname: Pentti
authors.affiliation: The Danish Aging Research Center and The Danish Twin Registry, Epidemiology, Biostatistics and Biodemography Unit, Department of Public Health, University of Southern Denmark, Odense, Denmark; Department of Psychology, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Matt
authors.initials: M
authors.lastname: McGue
authors.affiliation: The Danish Aging Research Center and The Danish Twin Registry, Epidemiology, Biostatistics and Biodemography Unit, Department of Public Health, University of Southern Denmark, Odense, Denmark; Department of Clinical Genetics, Odense University Hospital, Odense, Denmark; Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark.
authors.forename: Kaare
authors.initials: K
authors.lastname: Christensen
authors.affiliation: The Danish Aging Research Center and The Danish Twin Registry, Epidemiology, Biostatistics and Biodemography Unit, Department of Public Health, University of Southern Denmark, Odense, Denmark.
authors.forename: Lene
authors.initials: L
authors.lastname: Christiansen
mesh_terms: D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D003071:Cognition / Q000502:physiology; D056726:Genetic Association Studies; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D008136:Longevity / Q000235:genetics; D008875:Middle Aged; D012537:Scandinavian and Nordic Countries; D018433:Twin Studies as Topic
chemical_list: C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor
keywords: Aging; Alzheimers; Amyloid beta; Cognition; Dementia