Association of a neurokinin 3 receptor polymorphism with the anterior basal forebrain

The neuropeptide neurokinin 3 (NK3) and its receptor modulate cholinergic activity of the basal forebrain (BF) and are implicated in learning and memory. In Alzheimer's disease, the rs2765 single-nucleotide polymorphism (SNP) of the NK3 receptor-coding gene TACR3 was correlated with the right hippocampus volume. Here, we studied the association of the rs2765 SNP with magnetic resonance imaging-based volumes of the BF and hippocampus in a population-based sample of 1967 participants between 21 and 90 years of age. The rs2765 SNP was significantly associated with the most anterior BF volume corresponding to the medial septum/diagonal band, and with a significantly steeper age-related volume decline. The rs2765 SNP was not associated with other BF subvolumes or hippocampus volumes. Apolipoprotein E ε4 showed no correlation with any brain volume or global cognition. Our findings in a large population-based sample suggest an association of an NK3 receptor SNP with age-related decline of rostral cholinergic BF volume.