Peripheral blood markers in the diagnosis of Alzheimer' s disease

对141例临床诊断为阿尔茨海默病（AD）的患者（72.5±7.6岁）的空腹血浆同型半胱氨酸（pHcy）水平与139例年龄匹配的社区生活正常对照（正常对照，75.3±5.1岁）的空腹血浆同型半胱氨酸水平进行了比较。根据磁共振成像有无并发无症状脑梗死（SBI）将AD分为2个亚组。与正常对照组（11.0±3.0 μmol/L）和非SBI亚组（11.5±4.4 μmol/L）相比，SBI亚组pHcy水平（14.0±4.5 μmol/L）显著升高（0 <0.0001）。在调整年龄后，多元回归模型显示，高pHcy水平>11.4 μmol/L与AD患者发生SBI的风险增加相关（比值比4.2,95% c.i. 1.7-10.5, 0 =0.002）。其他血管危险因素，如性别。ApoE4基因、高血压、当前吸烟和血清胆固醇水平对SBI无显著影响。根据AD患者深部白质病变的严重程度，pHcy水平无显著差异。值得注意的是，发病年龄、认知功能、脑脊液tau或淀粉样蛋白β-肽1-42水平与AD患者的pHcy水平没有显著相关性。我们的研究结果表明，同型半胱氨酸可能不会导致AD的直接风险，但与共存的SBI有关，SBI是一种独立于其他血管风险发生的独特血管疾病。

Fasting plasma homocysteine (pHcy) levels in 141 patients with clinical diagnosis of Alzheimer' s disease (AD, 72.5±7.6 years) were compared with those in 139 age-matched community-dwelling normal control subjects (normal control, 75.3±5.1 years). When AD was grouped into 2 subgroups according to the presence or absence of co-existing silent brain infarction (SBI) on magnetic resonance imaging. the pHcy levels in the subgroup with SBI (14.0±4.5 μmol/L) were significantly elevated (o<0.0001) compared to the other subgroup without SBI (11.5±4.4 μmol) and the normal control group (11.0±3.0 μmol/L). After adjusting for age, multiple regression model demonstrated that high pHcy levels>11.4 μmol/L were associated with an increased risk for developing SBI in AD (odds ratio 4.2, 95% C. I. 1.7-10.5, o=0.002). Other vascular risk factors such as gender. ApoE4 gene, hypertension, current smoking, and serum cholesterol levels did not have a significant effect on SBI. The pHcy levels did not differ significantly according to the severity of deep white matter lesions among AD patients. Notably, either age at onset, cognitive function, cerebrospinal fluid tau or amyloid β-peptide1-42 levels did not significantly correlate with pHcy levels in AD. Our results suggest that homocysteine may not confer a direct risk for AD but relates to co-existing SBI, a unique vascular condition that occurs independently of other vascular risks.