It was also well documented by Petrov et al. [​166​] that HLD disrupted the BBB with limited transportation of glucose and insulin to the central nervous system, which provoked hyperinsulinemia to some extent can primarily stimulate deficiency of insulin in the brain, which down-regulates the expression of insulin-degrading enzyme and less accumulation of amyloid β-peptide [166]. Here, INS is linked to Hyperinsulinemia.