Engelborghs Sebastiaan, Maertens Karen, Vloeberghs Ellen, Aerts Tony, Somers Nore, Mariën Peter, De Deyn Peter P
Department of Neurology and Memory Clinic, Middelheim General Hospital (ZNA), Antwerp, Belgium.
Neurochem Int. 2006 Mar;48(4):286-95. doi: 10.1016/j.neuint.2005.11.002. Epub 2006 Jan 24.
To improve clinical, neuropsychological and behavioural characterisation of the cerebrospinal fluid (CSF) biomarkers beta-amyloid((1-42)) protein (Abeta42), protein tau (tau) and tau phosphorylated at threonine 181 (P-tau181) across diagnostic dementia categories, a prospective study was set up. Patients with probable Alzheimer's disease (AD) (n=201), AD with cerebrovascular disease (CVD) (AD+CVD) (n=33), frontotemporal dementia (FTD) (n=27), dementia with Lewy bodies (DLB) (n=22) and healthy controls (n=148) were included. All patients underwent neuropsychological examination and behavioural assessment by means of a battery of behavioural assessment scales. CSF was obtained by lumbar puncture and levels of Abeta42, tau and P-tau181 were determined with commercially available ELISA kits. Negative correlations between CSF Abeta42 levels and aggressiveness (Spearman: r=-0.223; p=0.002) and positive correlations with age at inclusion (r=0.195; p=0.006), age at onset (r=0.205; p=0.003) and MMSE scores (r=0.198; p=0.005) were found in AD. In AD+CVD, CSF Abeta42 levels were correlated with MMSE (r=0.482; p=0.006), Hierarchic Dementia Scale (r=0.503; p=0.017) and Boston Naming Test (r=0.516; p=0.012) scores. In controls, age was positively correlated with CSF tau (r=0.465; p<0.001) and P-tau181 levels (r=0.312; p<0.001). CSF tau and P-tau181 levels correlated significantly in all groups, whereas CSF Abeta42 correlated with tau and P-tau181 levels in healthy controls only. Negative correlations between CSF Abeta42 levels and aggressiveness were found in AD patients. CSF Abeta42 seems to be a stage marker for AD (+/-CVD) given the positive correlations with neuropsychological test results suggesting that CSF Abeta42 might be of help for monitoring disease progression. Different correlations between age and CSF biomarker levels were obtained in healthy controls compared to AD patients, indicating that AD-induced pathophysiological processes change age-dependent regulation of CSF biomarker levels.
为了改善脑脊液（CSF）生物标志物β-淀粉样蛋白（1-42）（Aβ42）、总tau蛋白（tau）和苏氨酸181位点磷酸化的tau蛋白（P-tau181）在不同诊断性痴呆类别中的临床、神经心理学及行为特征描述，开展了一项前瞻性研究。纳入了可能患有阿尔茨海默病（AD）的患者（n = 201）、合并脑血管疾病（CVD）的AD患者（AD + CVD）（n = 33）、额颞叶痴呆（FTD）患者（n = 27）、路易体痴呆（DLB）患者（n = 22）以及健康对照者（n = 148）。所有患者均通过一系列行为评估量表进行神经心理学检查和行为评估。通过腰椎穿刺获取脑脊液，使用市售酶联免疫吸附测定（ELISA）试剂盒测定Aβ42、tau和P-tau181的水平。在AD患者中，脑脊液Aβ42水平与攻击性呈负相关（斯皮尔曼相关系数：r = -0.223；p = 0.002），与纳入时年龄呈正相关（r = 0.195；p = 0.006）、发病年龄呈正相关（r = 0.205；p = 0.003）以及与简易精神状态检查表（MMSE）评分呈正相关（r = 0.198；p = 0.005）。在AD + CVD患者中，脑脊液Aβ^42水平与MMSE评分（r = 0.482；p = 0.006）、分级痴呆量表（r = 0.503；p = 0.017）和波士顿命名测试（r = 0.516；p = 0.012）评分相关。在对照者中，年龄与脑脊液tau水平呈正相关（r = 0.465；p < 0.001）以及与P-tau181水平呈正相关（r = 0.312；p < 0.001）。脑脊液tau和P-tau181水平在所有组中均显著相关，而脑脊液Aβ42仅在健康对照者中与tau和P-tau181水平相关。在AD患者中发现脑脊液Aβ42水平与攻击性呈负相关。鉴于脑脊液Aβ42与神经心理学测试结果呈正相关，提示其可能有助于监测疾病进展，脑脊液Aβ42似乎是AD（±CVD）的一个阶段标志物。与AD患者相比，健康对照者中年龄与脑脊液生物标志物水平的相关性不同，表明AD诱导的病理生理过程改变了脑脊液生物标志物水平的年龄依赖性调节。
