title: The Glu318Gly mutation of the presenilin-1 gene does not necessarily cause Alzheimer's disease.
abstract: In early-onset familial Alzheimer's disease (AD) pathogenic mutations have been found in the amyloid precursor protein (APP) gene and in the presenilin (PS)-1 and PS-2 genes. We screened for mutations in these genes in 20 patients with familial AD from the Finnish population. In addition, we sampled 41 sporadic AD patients and 59 controls to test for mutations identified in our familial AD cases. We detected an A-to-G transition in the PS-1 gene, resulting in a glutamic acid (Glu)-to-glycine (Gly) substitution at codon 318 in 2 familial and 2 sporadic AD patients. The Glu318Gly mutation has previously been reported to cause AD. We also found the Glu318Gly mutation in 4 healthy aged controls (range, 74-87 years). We thus conclude that the mutation is most likely a rare polymorphism not related to AD.
authors.affiliation: Karolinska Institute, Alzheimer's Disease Research Centre, KFC, Novum, Huddinge, Sweden.
authors.forename: K M
authors.initials: KM
authors.lastname: Mattila
authors.forename: C
authors.initials: C
authors.lastname: Forsell
authors.forename: T
authors.initials: T
authors.lastname: Pirttilä
authors.forename: J O
authors.initials: JO
authors.lastname: Rinne
authors.forename: T
authors.initials: T
authors.lastname: Lehtimäki
authors.forename: M
authors.initials: M
authors.lastname: Röyttä
authors.forename: L
authors.initials: L
authors.lastname: Lilius
authors.forename: A
authors.initials: A
authors.lastname: Eerola
authors.forename: P H
authors.initials: PH
authors.lastname: St George-Hyslop
authors.forename: H
authors.initials: H
authors.lastname: Frey
authors.forename: L
authors.initials: L
authors.lastname: Lannfelt
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D000595:Amino Acid Sequence / Q000235:genetics; D019943:Amino Acid Substitution / Q000235:genetics; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics; D001483:Base Sequence / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D053764:Presenilin-1
chemical_list: D016564:Amyloid beta-Protein Precursor; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1