Alzheimer’s and the X factor

US researchers have found a single nucleotide polymorphism (SNP) associated with increased risk of late-onset Alzheimer’s disease on the X chromosome, the first Alzheimer’s variant identified with gender-specific effects.

The SNP was located on the PCDH11X gene, which codes for a protocadherin involved in cell adhesion. Protocadherins are processed by presenilin proteins, mutations in which can cause early-onset forms of the disease.

The researchers conducted a genome-wide association study of 844 cases of late-onset Alzheimer’s and 1255 controls, backed up by a second group of 1547 cases and 1209 controls.

Women who had two copies of the SNP were at considerably higher risk of developing the disease than women with one copy or men. However, the researchers stress that the variant is very common and many women with two copies did not develop the disease.

“Compared to female non-carriers, the odds ratio was 1.75 for women with two copies of the variant and 1.26 for women with one copy,” senior investigator Steven Younkin, of the Mayo Clinic College of Medicine in Florida, said in a statement. “It was 1.18 for men with one copy compared to male non-carriers.”

These odds are much lower than those for the well-known ApoE4 allele, which has an odds ratio of 3.0, but are still significant, the researchers found.

Their findings were published online today in Nature Genetics.