title: A novel alternative splice variant of nicastrin and its implication in Alzheimer disease.
abstract: Nicastrin interacts with gamma-secretase complex components predominantly via the N-terminal third of the transmembrane domain. The authentic transmembrane domain is critically required for the interaction with gamma-secretase complex components and for formation of an active gamma-secretase complex. In this study, we have identified a novel alternatively spliced transcript of nicastrin in human brain tissue. This transcript (NCSTN-DeltaE16) lacks exon 16 of nicastrin mRNA, which leads to deletion of 71 amino acids just upstream of its transmembrane domain. Its expression pattern was analyzed in the hippocampus of patients with pathologically diagnosed Alzheimer disease (cases) and non-Alzheimer dementia (controls). In patients with the APOE-epsilon4 allele, the frequency of Alzheimer disease appeared to be increased in the NCSTN-DeltaE16-positive group, but the association was not statistically significant. In conclusion, the expression of NCSTN-DeltaE16 transcript may confer some additional risk for developing Alzheimer disease beyond the risk due to ApoE-epsilon4 allele. Further investigation in larger scale population would be necessary to address its potential implication in Alzheimer disease.
authors.affiliation: Department of Integrated Basic Medical Science, School of Medicine, Ehime University, Shitsukawa, Toon, Ehime 791-0295, Japan. mitsuda@m.ehime-u.ac.jp
authors.forename: Noriaki
authors.initials: N
authors.lastname: Mitsuda
authors.forename: Hidehisa D
authors.initials: HD
authors.lastname: Yamagata
authors.forename: Wangtao
authors.initials: W
authors.lastname: Zhong
authors.forename: Mamoru
authors.initials: M
authors.lastname: Aoto
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Akatsu
authors.forename: Natsuko
authors.initials: N
authors.lastname: Uekawa
authors.forename: Kouzin
authors.initials: K
authors.lastname: Kamino
authors.forename: Keiko
authors.initials: K
authors.lastname: Taguchi
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Maruyama
authors.forename: Kenji
authors.initials: K
authors.lastname: Kosaka
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Takeda
authors.forename: Ikuko
authors.initials: I
authors.lastname: Kondo
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Miki
mesh_terms: D017668:Age of Onset; D000368:Aged; D017398:Alternative Splicing / Q000235:genetics*; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D053829:Amyloid Precursor Protein Secretases; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001923:Brain Chemistry / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D009929:Organ Size; D012313:RNA; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D008562:Membrane Glycoproteins; C034477:RNA primers; C413604:nicastrin protein; D012313:RNA; D053829:Amyloid Precursor Protein Secretases