Female-specific genetic risk factor for Alzheimer’s disease

A variant in a gene on the X chromosome is associated with increased risk of Alzheimer’s disease specifically in women, according to a study published online this week in Nature Genetics. This is the first evidence for a sex-specific genetic risk factor for this disease.

Late-onset Alzheimer’s disease is a neurodegenerative disorder and is the most common cause of dementia in the elderly. Variation in the gene APOE is the only consistently replicated genetic risk factor known. Steven Younkin and colleagues carry out a genome-wide association study of individuals with Alzheimer’s disease, and identify a variant in the gene PCDH11X as associated with susceptibility to the disease with a high degree of statistical significance. When the authors analyzed the data accounting for sex, they found that the association was almost entirely restricted to women. PCDH11X encodes a protein called a protocadherin, which is part of a family of molecules that promote cell-cell adhesion and signaling in the central nervous system. Some evidence suggests that protocadherins may be split to an active form by an enzyme linked to early-onset forms of Alzheimer’s disease.