Nicastrin gene in familial and sporadic Alzheimer's disease

• Published in: Neuroscience letters Vol. 353; no. 1; pp. 61 - 65
• Main Authors: Confaloni, Annamaria, Terreni, Liana, Piscopo, Paola, Crestini, Alessio, Campeggi, Lorenzo Malvezzi, Frigerio, Carlo Sala, Blotta, Ida, Perri, Maria, Di Natale, Manuela, Maletta, Raffaele, Marcon, Gabriella, Franceschi, Massimo, Bruni, Amalia C, Forloni, Gianluigi, Cantafora, Alfredo
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 15.12.2003; Elsevier
• Subjects: Age of Onset; Aged; Aged, 80 and over; Alzheimer Disease - classification; Alzheimer Disease - genetics; Alzheimer's disease; Amyloid precursor protein; Amyloid Precursor Protein Secretases; Apolipoprotein E4; Apolipoproteins E - genetics; Asparagine - genetics; Biological and medical sciences; Case-Control Studies; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Female; Genotype; Humans; Male; Medical sciences; Membrane Glycoproteins - genetics; Missense mutation; Mutation, Missense; Neurology; Polymorphism, Single-Stranded Conformational; Presenilin; Reverse Transcriptase Polymerase Chain Reaction - methods; RNA, Messenger - biosynthesis; Single nucleotide polymorphism; Tyrosine - genetics; β-Amyloid; β-Amyloid; Presenilin; Missense mutation; Single nucleotide polymorphism; Alzheimer's disease; Amyloid precursor protein; Human; Nervous system diseases; Sporadic; Alzheimer disease; Cerebral disorder; Familial disease; β Amyloid protein; Central nervous system disease; Degenerative disease
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2003.09.007

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.