Gender-linked Alzheimer's gene discovered

Researchers at the Mayo Clinic College of Medicine have discovered a gene variant located on the X chromosome that is linked to late-onset Alzheimer's disease (LOAD).

Steven Younkin and colleagues detected a variant in the gene PCDH11X, which appeared to increase susceptibility to LOAD, whilst studying the genome of 844 people with Alzheimer's disease and 1,255 non-demented people. Further investigation revealed that women who inherited two copies of the PCDH11X variant were at considerably greater risk of developing LOAD. Women with a variant on one of their two X chromosomes had a slightly increased risk of LOAD, as did men who carried the variant on their single X chromosome, but this increased risk was not statistically significant in men.

PCDH11X encodes for a protein called a protocadherin, part of a family of molecules that promote cell-cell adhesion and aids cell signaling in the central nervous system. Previous research has suggested that protocadherins are processed by another group of proteins called presenilins, mutations in presenilin genes are linked to early-onset familial forms of Alzheimer's disease.

“When we set out to scan the genome for Alzheimer's disease susceptibility genes, we were not at all certain that we would find any gene other than the well-established APOE gene,” says Minerva Carrasquillo, Ph.D.  “Fortunately, the unbiased genome-wide scan that we undertook enabled us to identify PCDH11X, a previously unsuspected gene on the X chromosome that is the first to show gender-specific effects.”

Carrasquillo MM, Zou F, Pankratz VS, et al. Genetic variation in PCDH11X is associated with susceptibility to late-onset Alzheimer's disease. Nature Genetics. Published online: 11 January 2009. doi:10.1038/ng.305

News release: Mayo Clinic Researchers Find that Variants in a Gene on the X Chromosome are Associated with Increased Susceptibility to Alzheimer's Disease. Mayo Clinic. January 11th 2009.