Title : A polymorphism in
CALHM1 influences
Ca2 + homeostasis,
Abeta levels, and Alzheimer's disease risk
Abstract :
- Alzheimer's disease (AD) is a genetically heterogeneous disorder characterized by early hippocampal atrophy and cerebral amyloid-beta ( Abeta ) peptide de position
- 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 Ca(2 +) concentrations and Abeta levels
- CALHM1 homomultimerizes, shares strong sequence similarities with the selectivity filter of the NMDA receptor , and generates a large Ca(2 +) 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 x 10 (-10))
- We further found that the P86L polymorphism increases Abeta levels by interfering with CALHM1-mediated Ca(2 +) permeability
- We propose that CALHM1 encodes an essential component of a previously uncharacterized cerebral Ca(2 +) channel that controls Abeta levels and susceptibility to late-onset AD
Output (sent_index, trigger,
protein,
sugar,
site):
- 3. glycoprotein, , CALHM1, -, -
- 3. glycoprotein, , glycoprotein, -, -
Output(Part-Of) (sent_index,
protein,
site):
*Output_Site_Fusion* (sent_index,
protein,
sugar,
site):