Oikonomidi Aikaterini, Lewczuk Piotr, Kornhuber Johannes, Smulders Yvo, Linnebank Michael, Semmler Alexander, Popp Julius
Department of Psychiatry, Division of Old Age Psychiatry, University Hospital of Lausanne, Lausanne, Switzerland.
Department of Psychiatry and Psychotherapy, University of Erlangen, Erlangen, Germany.
J Neurochem. 2016 Oct;139(2):324-332. doi: 10.1111/jnc.13766. Epub 2016 Sep 30.
Disturbed homocysteine metabolism may contribute to amyloidogenesis by modulating the amyloid precursor protein (APP) production and processing. The objective of this study was to investigate the relationships between cerebral amyloid production and both blood and cerebrospinal fluid (CSF) markers of the homocysteine metabolism. We assessed CSF concentrations of soluble APPα, soluble APPβ, and amyloid β1-42 (Aβ1-42), as well as plasma levels of homocysteine (Hcys), total vitamin B12, and folate, and CSF concentrations of homocysteine (Hcys-CSF), 5-methyltetrahydrofolate (5-MTHF), S-adenosylmethionine (SAM), and S-adenosylhomocysteine (SAH) in 59 subjects with normal cognition. Linear regression analyses were performed to assess associations between homocysteine metabolism parameters and amyloid production. The study was approved by the Ethical Committee of the University of Bonn. After controlling for age, gender, APOEe4 status, and albumin ratio (Qalb), higher Aβ1-42 CSF levels were associated with high Hcys and low vitamin B12 plasma levels as well as with high Hcys, high SAH, and low 5-MTHF CSF levels. Higher CSF concentrations of sAPPα and sAPPβ were associated with high SAH levels. The results suggest that disturbed homocysteine metabolism is related to increased CSF levels of sAPP forms and Aβ1-42, and may contribute to the accumulation of amyloid pathology in the brain. Disturbed homocysteine metabolism may contribute to amyloidogenesis by modulating the amyloid precursor protein (APP) production and processing. We found associations between CSF levels of soluble APP forms and Aβ1-42, and markers of the homocysteine metabolism in both plasma and CSF in adults with normal cognition. Disturbed homocysteine metabolism may represent a target for preventive and early disease-modifying interventions in Alzheimer's disease.
同型半胱氨酸代谢紊乱可能通过调节淀粉样前体蛋白（APP）的产生和加工过程，促进淀粉样蛋白生成。本研究的目的是探讨脑淀粉样蛋白生成与同型半胱氨酸代谢的血液和脑脊液（CSF）标志物之间的关系。我们评估了59名认知正常受试者脑脊液中可溶性APPα、可溶性APPβ和淀粉样β1-42（Aβ1-42）的浓度，以及血浆中同型半胱氨酸（Hcys）、总维生素B12和叶酸的水平，还有脑脊液中同型半胱氨酸（Hcys-CSF）、5-甲基四氢叶酸（5-MTHF）、S-腺苷甲硫氨酸（SAM）和S-腺苷同型半胱氨酸（SAH）的浓度。进行线性回归分析以评估同型半胱氨酸代谢参数与淀粉样蛋白生成之间的关联。该研究获得了波恩大学伦理委员会的批准。在控制年龄、性别、APOEe4状态和白蛋白比率（Qalb）后，较高的脑脊液Aβ1-42水平与高血浆Hcys水平、低血浆维生素B12水平以及高脑脊液Hcys水平、高脑脊液SAH水平和低脑脊液5-MTHF水平相关。较高的脑脊液sAPPα和sAPPβ浓度与高脑脊液SAH水平相关。结果表明，同型半胱氨酸代谢紊乱与脑脊液中sAPP形式和Aβ1-42水平升高有关，可能导致大脑中淀粉样病理的积累。同型半胱氨酸代谢紊乱可能通过调节淀粉样前体蛋白（APP）的产生和加工过程，促进淀粉样蛋白生成。我们发现，在认知正常的成年人中，脑脊液中可溶性APP形式和Aβ1-42的水平与血浆和脑脊液中的同型半胱氨酸代谢标志物之间存在关联。同型半胱氨酸代谢紊乱可能是阿尔茨海默病预防性和早期疾病修饰干预的一个靶点。
