Porcellini E, Davis E J, Chiappelli M, Ianni E, Di Stefano G, Forti P, Ravaglia G, Licastro F
Department of Experimental Pathology, School of Medicine, University of Bologna, Via S. Giacomo 14, 40126 Bologna, Italy.
Curr Pharm Des. 2008;14(26):2659-64. doi: 10.2174/138161208786264151.
alpha-1-antichymotrypsin (ACT), is an acute phase protein and a protease inhibitor produced by the liver and brain. ACT is involved in the pathogenesis of Alzheimer's disease (AD), since elevated ACT concentration was found in cerebrospinal fluid (CSF) and brain from AD. ACT has also been shown to influence amyloid deposition in vitro and in animal models of AD. In this investigation 830 healthy controls, 69 subjects with cognitive impairment and not dementia (CIND), 53 patients with severe clinical AD and 142 patients with mild AD were investigated. Plasma levels of ACT were measured with a new competitive immune enzyme linked immune-assay (ELISA). ACT levels were higher in AD patients than in CIND or controls. An age dependent increase of plasma ACT was present in both healthy elderly and CIND. Patients with mild clinical AD were followed up for two years and stratified according to the rate of clinical deterioration. CT plasma levels were elevated in AD patients that showed an accelerated rate of cognitive deterioration during the follow up; this increment being prominent in AD with the Apolipoprotein E (APOE) epsilon 4 allele. Therefore, increased peripheral ACT levels in APOE 4 positive patients appear to predict an accelerated clinical progression. Plasma ACT might be used as a surrogate marker to monitor the conversion of pre-dementia stages to AD and the progression of the disease. The development of compounds able to interfere with the ACT biological activity (protease inhibition and/or promotion of amyloid deposition) might have therapeutic relevance for the disease.
α-1-抗糜蛋白酶（ACT）是一种急性期蛋白，由肝脏和大脑产生的蛋白酶抑制剂。ACT参与阿尔茨海默病（AD）的发病机制，因为在AD患者的脑脊液（CSF）和大脑中发现ACT浓度升高。在体外和AD动物模型中，ACT也被证明会影响淀粉样蛋白沉积。在这项研究中，对830名健康对照者、69名有认知障碍但未患痴呆症（CIND）的受试者、53名重度临床AD患者和142名轻度AD患者进行了调查。采用一种新的竞争性免疫酶联免疫分析法（ELISA）测定血浆ACT水平。AD患者的ACT水平高于CIND患者或对照组。健康老年人和CIND患者的血浆ACT均随年龄增长而升高。对轻度临床AD患者进行了两年随访，并根据临床恶化率进行分层。在随访期间认知恶化加速的AD患者中，血浆ACT水平升高；这种升高在携带载脂蛋白E（APOE）ε4等位基因的AD患者中尤为明显。因此，APOE 4阳性患者外周ACT水平升高似乎预示着临床进展加速。血浆ACT可作为替代标志物，用于监测痴呆前期向AD的转变以及疾病的进展。开发能够干扰ACT生物学活性（蛋白酶抑制和/或促进淀粉样蛋白沉积）的化合物可能对该疾病具有治疗意义。
