Ghrelin cascade changes in the peripheral blood of Japanese patients with Alzheimer's disease.

The neuroprotective effect of ghrelin has recently been reported in Alzheimer's disease (AD). Ghrelin is converted from des-acyl ghrelin to the activated form, acyl ghrelin, by membrane bound o-acyltransferase 4 (MBOAT4), and then binds to growth hormone secretagogue receptor (GHS-R). We examined the levels of plasma acyl/des-acyl ghrelin in 75 AD subjects and age- and sex-matched controls, as well as the DNA methylation and mRNA expression of MBOAT4 and GHS-R in peripheral leukocytes. The acyl ghrelin concentration was significantly higher in AD subjects than in controls (2.18 ± 1.25 vs. 1.49 ± 2.3, p = 0.001). The methylation rate of MBOAT4 CpG 2 was significantly lower in AD subjects than in controls (4.0 ± 0.9 vs. 4.7 ± 1.2, p < 0.001). The mRNA expression levels of MBOAT4 and GHS-R1b were significantly higher in AD subjects than in controls (MBOAT4: 1.10 ± 0.48 vs. 1.0 ± 0.55, p = 0.049; GHS-R1b: 1.76 ± 3.18 vs. 1.0 ± 1.56, p = 0.030). These changes in the ghrelin cascade in peripheral blood may reflect those in the brain, and may be a neuroprotective biomarker in AD.