title: Nicastrin gene in familial and sporadic Alzheimer's disease.
abstract: Nicastrin is a protein recently discovered associated to presenilins and involved in the production of amyloid beta peptide that accumulates in Alzheimer's disease (AD) brain. In this study the nicastrin gene was examined for unknown mutations and polymorphisms in 104 patients with familial AD (52 early-onset and 52 late-onset), 174 sporadic AD and 191 healthy neurological controls of Italian origin. The scanning of the nicastrin gene identified a missense mutation (N417Y) in two patients with sporadic AD, in an early-onset familial AD and in a young control subject. Furthermore, we found two silent mutations and four intronic polymorphisms, three of them co-segregating in a single haplotype. We found some differences in the distribution of genotype alterations in the AD population compared to the controls. However, our data together with other evidence did not support the pathological role of missense mutation N417Y.
authors.affiliation: Laboratory of Metabolism, Istituto Superiore di Sanità, 00161 Rome, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Confaloni
authors.forename: Liana
authors.initials: L
authors.lastname: Terreni
authors.forename: Paola
authors.initials: P
authors.lastname: Piscopo
authors.forename: Alessio
authors.initials: A
authors.lastname: Crestini
authors.forename: Lorenzo Malvezzi
authors.initials: LM
authors.lastname: Campeggi
authors.forename: Carlo Sala
authors.initials: CS
authors.lastname: Frigerio
authors.forename: Ida
authors.initials: I
authors.lastname: Blotta
authors.forename: Maria
authors.initials: M
authors.lastname: Perri
authors.forename: Manuela
authors.initials: M
authors.lastname: Di Natale
authors.forename: Raffaele
authors.initials: R
authors.lastname: Maletta
authors.forename: Gabriella
authors.initials: G
authors.lastname: Marcon
authors.forename: Massimo
authors.initials: M
authors.lastname: Franceschi
authors.forename: Amalia C
authors.initials: AC
authors.lastname: Bruni
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Forloni
authors.forename: Alfredo
authors.initials: A
authors.lastname: Cantafora
mesh_terms: D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000145:classification / Q000235:genetics*; D053829:Amyloid Precursor Protein Secretases; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics; D001216:Asparagine / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D020125:Mutation, Missense; D018807:Polymorphism, Single-Stranded Conformational; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014443:Tyrosine / Q000235:genetics
chemical_list: D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; C413604:nicastrin protein; D014443:Tyrosine; D001216:Asparagine; D053829:Amyloid Precursor Protein Secretases