Urinary Homocysteic Acid Levels Correlate with Mini-Mental State Examination Scores in Alzheimer's Disease Patients
Urinary Homocysteic Acid Levels Correlate with Mini-Mental State Examination Scores in Alzheimer's Disease Patients
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DOI：
10.3233/jad-2012-120022
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发表时间：
2012-01-01
影响因子：
4
通讯作者：
Tabira, Takeshi
中科院分区：
文献类型：
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作者：
Hasegawa, Tohru;Ichiba, Masayoshi;Tabira, Takeshi
同型半胱氨酸（HA）已被认为是阿尔茨海默病（AD）小鼠模型3xTg-AD的病原体。然而，目前尚不清楚HA是否与人类有关。我们研究了AD患者（n = 70）和非AD对照组（n = 34）尿HA水平与MMSE评分之间的关系。我们发现两个变量（尿HA水平和MMSE评分）之间呈正相关，具有统计学意义（r = 0.31, p = 0.0008, n = 70）。这种相关性在女性中强于男性（r = 0.43, p = 0.005, n = 44; r = 0.48, p = 0.02, n = 22）。AD患者尿HA水平与对照组比较差异有统计学意义（AD: 8.7 +/- 7.5, n = 70；非痴呆对照组：13.3 +/- 9.4,n = 34, p < 0.01）。此外，年龄和吸烟被发现是降低尿HA水平的因素。我们的初步研究显示血HA（微摩尔）与尿HA水平呈负相关（r = -0.6, p = 0.007, n = 19），血HA水平与MMSE评分呈负相关（r = -0.79, p = 0.0000518, n = 19）。基于这些结果，我们推测尿排泄减少导致血凝素水平升高，从而导致认知功能障碍。本研究也提示透明质酸可能是尿毒症脑病的一种候选神经毒素。由于淀粉样蛋白- β增加了HA毒性，而HA是n -甲基- d-天冬氨酸（NMDA）受体的激动剂，我们推测血HA升高通过NMDA受体介导的AD毒性影响大脑认知功能。
Homocysteic acid (HA) has been suggested as a pathogen in a mouse model of Alzheimer's disease (AD), 3xTg-AD. However, it is not established whether HA is involved in humans. We investigated the relationship between urinary HA levels and Mini-Mental State Examination (MMSE) scores in AD patients (n = 70) and non-AD controls (n = 34). We found a positive, statistically significant relationship between the two variables (the urinary HA level and MMSE score) (r = 0.31, p = 0.0008, n = 70). This relationship was stronger in females than males (r = 0.43, p = 0.005, n = 44 in females; r = 0.48, p = 0.02, n = 22 in males). The urinary HA levels were significantly different in AD patients than controls (AD: 8.7 +/- 7.5, n = 70; non-dementia control: 13.3 +/- 9.4, n = 34, p < 0.01). In addition, aging and smoking were found as lowering factors for urinary HA levels. Our preliminary study showed a negative, statistically significant relationship between blood HA (micromole) and urine HA levels (r = -0.6, p = 0.007, n = 19), and between blood HA levels and MMSE scores (r = -0.79, p = 0.0000518, n = 19). On the basis of these results, we speculate that reduced urinary excretion induces elevated HA levels in blood, resulting in cognitive dysfunctions. This study also suggests that HA may be a candidate of neurotoxins for uremic encephalopathy. Since amyloid-beta increases HA toxicity and HA is an agonist of N-methyl-D-aspartic acid (NMDA) receptor, we speculate that elevated blood HA affects the brain cognitive function through NMDA receptor-mediated toxicity in AD.