Idiopathic Normal Pressure Hydrocephalus has a Different Cerebrospinal Fluid Biomarker Profile from Alzheimer's Disease
Idiopathic Normal Pressure Hydrocephalus has a Different Cerebrospinal Fluid Biomarker Profile from Alzheimer's Disease
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DOI：
10.3233/jad-142622
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发表时间：
2015-01-01
影响因子：
4
通讯作者：
Kinoshita, Ayae
中科院分区：
文献类型：
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作者：
Jingami, Naoto;Asada-Utsugi, Megumi;Kinoshita, Ayae
特发性常压脑积水（iNPH）的诊断有时伴随阿尔茨海默病（AD）病理。本研究的目的是确定iNPH特异性脑脊液（CSF）生物标志物动力学，并评估其区分iNPH和AD的能力。在93个连续的脑脊液样本中测量了总tau （t-tau）、苏氨酸181磷酸化的tau （p-tau）、淀粉样蛋白- β (A β) 42和40以及富含亮氨酸的α -2糖蛋白（LRG），这些样本包括55个iNPH（46个tap试验应答者）、20个AD、11个皮质基底综合征和7个脊髓小脑病。与AD相比，iNPH患者的t-tau和p-tau水平显著降低，尤其是tap试验应答者。迷你精神状态检查得分与AD （R = 0.44）和iNPH （R = 0.28）的A β值（42）之间存在相关性。尽管A β(42/40)比值在iNPH和AD之间无显著差异（p = 0.08），但A β(40)和A β(42)水平在iNPH中呈正相关（R = 0.73），而在AD中呈负相关（R = 0.26），提示它们具有离散的淀粉样蛋白清除和病理。两者之间的LRG水平没有差异。因此，我们的研究表明，尽管iNPH患者的脑脊液生物标志物可能受到伴随的tau和/或淀粉样蛋白病理的影响，但脑脊液t-tau和p-tau对iNPH和AD的分化非常有用。
The diagnosis of idiopathic normal pressure hydrocephalus (iNPH) is sometimes complicated by concomitant Alzheimer's disease (AD) pathology. The purpose of the present study is to identify an iNPH-specific cerebrospinal fluid (CSF) biomarker dynamics and to assess its ability to differentiate iNPH from AD. Total tau (t-tau), tau phosphorylated at threonine 181 (p-tau), amyloid-beta (A beta) 42 and 40, and leucine-rich alpha-2-glycoprotein (LRG) were measured in 93 consecutive CSF samples consisting of 55 iNPH (46 tap test responders), 20 AD, 11 corticobasal syndrome, and 7 spinocerebeller disease. Levels of t-tau and p-tau were significantly decreased in iNPH patients especially in tap test responders compared to AD. Correlation was observed between Mini-Mental State Examination scores and A beta(42) in AD (R = 0.44) and mildly in iNPH (R = 0.28). Although A beta(42/40) ratio showed no significant difference between iNPH and AD (p = 0.08), the levels of A beta(40) and A beta(42) correlated positively with each other in iNPH (R = 0.73) but much less in AD (R = 0.26), suggesting that they have discrete amyloid clearance and pathology. LRG levels did not differ between the two. Thus, our study shows that although CSF biomarkers of iNPH patients can be affected by concomitant tau and/or amyloid pathology, CSF t-tau and p-tau are highly useful for differentiation of iNPH and AD.