Brain receptor gene activity linked to lower Alzheimer’s risk

An analysis of human genetic data examined links between Alzheimer’s disease and activity of the gene for the glucagon-like peptide-1 receptor, a protein that responds to a hormone. Researchers used Mendelian randomization, a method that uses inherited genetic differences to assess associations. They analysed genetic variants linked to gene activity in blood and the brain’s cortex, its outer layer.

Receptor gene activity was associated with lower Alzheimer’s risk and lower levels of phosphorylated tau, a chemically modified protein, in fluid around the brain and spinal cord. Among 11 metabolic and inflammatory factors, systolic blood pressure—the pressure when the heart contracts—was the only independent intermediary identified. The link with lower disease risk remained after accounting for these factors. Further analyses attributed the association predominantly to gene activity in the cortex rather than blood.