Record number :
1019303
Title of article :
A Polymorphism in CALHM1 Influences Ca2+ Homeostasis, Aβ Levels, and Alzheimerʹs Disease Risk
Author/Authors :
Ute Dreses-Werringloer، نويسنده , , Jean-Charles Lambert، نويسنده , , Valérie Vingtdeux، نويسنده , , Haitian Zhao، نويسنده , , Horia Vais، نويسنده , , Adam Siebert، نويسنده , , Ankit Jain، نويسنده , , Jeremy Koppel، نويسنده , , Anne Rovelet-Lecrux، نويسنده , , Didier Hannequin، نويسنده , , Florence Pasquier، نويسنده , , Daniela Galimberti، نويسنده , , Elio scarpini، نويسنده , , David Mann، نويسنده , , Corinne Lendon، نويسنده , , Dominique Campion، نويسنده , , Philippe Amouyel، نويسنده , , Peter Davies، نويسنده , , J. Kevin Foskett، نويسنده , , Fabien Campagne، نويسنده , , et al.، نويسنده ,
Issue Information :
هفته نامه با شماره پیاپی سال 2008
Pages :
13
From page :
1149
To page :
1161
Abstract :
Alzheimerʹs disease (AD) is a genetically heterogeneous disorder characterized by early hippocampal atrophy and cerebral amyloid-β (Aβ) peptide deposition. Using TissueInfo to screen for genes preferentially expressed in the hippocampus and located in AD linkage regions, we identified a gene on 10q24.33 that we call CALHM1. We show that CALHM1 encodes a multipass transmembrane glycoprotein that controls cytosolic Ca2+ concentrations and Aβ levels. CALHM1 homomultimerizes, shares strong sequence similarities with the selectivity filter of the NMDA receptor, and generates a large Ca2+ conductance across the plasma membrane. Importantly, we determined that the CALHM1 P86L polymorphism (rs2986017) is significantly associated with AD in independent case-control studies of 3404 participants (allele-specific OR = 1.44, p = 2 × 10−10). We further found that the P86L polymorphism increases Aβ levels by interfering with CALHM1-mediated Ca2+ permeability. We propose that CALHM1 encodes an essential component of a previously uncharacterized cerebral Ca2+ channel that controls Aβ levels and susceptibility to late-onset AD.
Journal title :
CELL
Serial Year :
2008
Link To Document :
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