Nicastrin gene in familial and sporadic Alzheimer's disease.
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.
Confaloni
Annamaria
A
Laboratory of Metabolism, Istituto Superiore di Sanità, 00161 Rome, Italy.
Terreni
Liana
L
Piscopo
Paola
P
Crestini
Alessio
A
Campeggi
Lorenzo Malvezzi
LM
Frigerio
Carlo Sala
CS
Blotta
Ida
I
Perri
Maria
M
Di Natale
Manuela
M
Maletta
Raffaele
R
Marcon
Gabriella
G
Franceschi
Massimo
M
Bruni
Amalia C
AC
Forloni
Gianluigi
G
Cantafora
Alfredo
A
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
D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; C413604:nicastrin protein; D014443:Tyrosine; D001216:Asparagine; D053829:Amyloid Precursor Protein Secretases