Hyperhomocysteinemia is a closely independent risk factor for AD because homocysteine can increase neuronal cell apoptosis and inhibit the production of endogenous H2S. Moreover, homocysteine causes the upregulation of ERS-related GRP78, CHOP, and cleaved caspase-12 (Wei et al., 2014). The gene discussed is HSPA5; the disease is Alzheimer disease.