Department of Neurology, Methodist Neurological Institute, Institute for Academic Medicine Houston Methodist Research Institute, Houston Methodist Hospital, Houston, TX 77030, USA.
Weill Cornell Medical College, Department of Neurology, Cornell University, New York, NY 10065, USA.
Int J Mol Sci. 2019 Jan 14;20(2):319. doi: 10.3390/ijms20020319.
DNA methylation and other epigenetic factors are important in the pathogenesis of late-onset Alzheimer's disease (LOAD). Methylenetetrahydrofolate reductase () gene mutations occur in most elderly patients with memory loss. MTHFR is critical for production of S-adenosyl-l-methionine (SAM), the principal methyl donor. A common mutation (1364T/T) of the cystathionine-γ-lyase () gene affects the enzyme that converts cystathionine to cysteine in the transsulfuration pathway causing plasma elevation of total homocysteine (tHcy) or hyperhomocysteinemia-a strong and independent risk factor for cognitive loss and AD. Other causes of hyperhomocysteinemia include aging, nutritional factors, and deficiencies of B vitamins. We emphasize the importance of supplementing vitamin B (methylcobalamin), vitamin B₉ (folic acid), vitamin B₆ (pyridoxine), and SAM to patients in early stages of LOAD.
DNA 甲基化和其他表观遗传因素在迟发性阿尔茨海默病 (LOAD) 的发病机制中起重要作用。亚甲基四氢叶酸还原酶 () 基因突变发生在大多数有记忆丧失的老年患者中。MTHFR 对于 S-腺苷甲硫氨酸 (SAM) 的产生至关重要，SAM 是主要的甲基供体。胱硫醚-γ-裂解酶 () 基因的常见突变 (1364T/T) 影响将胱硫醚转化为半胱氨酸的酶，导致转硫途径中血浆总同型半胱氨酸 (tHcy) 或高同型半胱氨酸血症升高 - 认知丧失和 AD 的一个强烈且独立的危险因素。高同型半胱氨酸血症的其他原因包括衰老、营养因素和 B 族维生素缺乏。我们强调在 LOAD 的早期阶段向患者补充维生素 B（甲钴胺）、维生素 B₉（叶酸）、维生素 B₆（吡哆醇）和 SAM 的重要性。
