Error in CALHM1 Gene Linked to Alzheimer's Disease
SNP in gene, which controls cytosolic calcium ion levels, promotes Aβ accumulation
FRIDAY, June 27 (HealthDay News) -- A single-nucleotide polymorphism in the gene CALHM1, found on chromosome 10, may increase the risk of late-onset Alzheimer's disease, researchers report in the June 27 issue of Cell.
Ute Dreses-Werringloer, Ph.D., of the Feinstein Institute for Medical Research in Manhasset, N.Y., and colleagues screened for genes predominantly expressed in the hippocampus and found in linkage regions for late-onset Alzheimer's disease using TissueInfo and the Alzgene database. They identified CALHM1, which controls cytosolic levels of calcium ion Ca2+ and has sequence similarities with the predicted selectivity filter of the N-methyl-D-aspartate receptor.
The investigators found that the frequency of the polymorphism P86L was increased in cases of Alzheimer's disease in five cohorts. It inhibits plasma membrane Ca2+ permeability, lowers cytosolic Ca2+ and promotes amyloid-beta (Aβ) accumulation, the researchers report.
"The present work provides strong support for the Ca2+ hypothesis of Alzheimer's disease and is also an important step toward understanding the potential pathological cross talk between Ca2+ signaling disturbances and pathways of Aβ accumulation. Moreover, the identification of CALHM1 as a key modulator of Ca2+ homeostasis will allow us to further dissect the precise mechanism by which cytosolic Ca2+ modulates amyloid precursor protein metabolism," the authors write.