It has been reported that these substances are also produced by astrocytes and that protein expression of SPINT1 is weak in the AD brain [36] so if we postulate that changes in DNA methylation levels similar to those in the blood also occur in the brain, this would be consistent with the increased methylation in the SPINT1 gene promoter region of AD subjects in the present study. Here, SPINT1 is linked to Alzheimer disease.