老年痴呆症早期贝塔分泌酶升高
旅美华人科学家申勇领导的国际研究小组5日报告说，老年痴呆症发病早期，患者脑脊液里的贝塔分泌酶显著升高，这一发现有助于老年痴呆症的早期诊断。
美国老年病研究所分子细胞实验室主任申勇领导的研究小组，由美国、德国、瑞典等多国科学家组成。他们对大约300个老年痴呆症病例进行临床研究后发现，在老年痴呆症发病早期，也就是病人刚刚出现轻微记忆力和智力下降时，病人脑脊液里的贝塔分泌酶就已显著升高。贝塔分泌酶是产生贝塔淀粉状蛋白的关键酶。
这项研究成果已发表在美国《普通精神病学文献》月刊上。
此前，申勇领导的另外一个研究小组曾在《自然－医学》杂志上发表论文说，老年痴呆症并非基因突变所致，而是大量贝塔淀粉状蛋白在脑内形成块状沉淀造成的。研究人员说，找到一种可靠、客观的生物标记准确诊断老年痴呆症，对于尽早采取有效治疗手段具有重要意义。
老年痴呆症是影响老年人健康的顽症。美国《普通精神病学文献》提供的资料显示，全世界60岁以上老年人中约有10％患有此病。（生物谷援引新华网）
原始出处:
Arch Gen Psychiatry，Vol. 64 No. 6, June 2007
Levels of 
-Secretase (BACE1) in Cerebrospinal Fluid as a Predictor of Risk in Mild Cognitive Impairment
Zhenyu Zhong, MSc; Michael Ewers, MD; Stefan Teipel, MD; Katharina Bürger, MD; Anders Wallin, MD; Kaj Blennow, MD; Ping He, PhD; Carrie McAllister, BSc; Harald Hampel, MD; Yong Shen, MD, PhD
Arch Gen Psychiatry. 2007;64:718-726.
Context Elevated 
-secretase (-site amyloid precursor protein–cleaving enzyme 1 [BACE1]) activity has been found in the brains of patients with sporadic Alzheimer disease (AD) compared with controls. Now we are particularly interested in whether BACE1 can be identified in the cerebrospinal fluid (CSF) of patients with mild cognitive impairment (MCI), a population at high risk for AD. The possible presence of BACE1 in the CSF of patients with AD and MCI has so far gone unreported.
Objective To examine whether BACE1 can be identified in the CSF of patients with MCI.
Design We evaluated CSF BACE1 levels using 2 sandwich enzyme-linked immunosorbent assays, BACE1 enzymatic activities by means of synthetic fluorescence substrate, and total amyloid- peptide levels using a sandwich enzyme-linked immunosorbent assay.
Setting Two independent research centers.
Participants Eighty patients with sporadic AD, 59 patients with MCI, and 69 controls.
Main Outcome Measures BACE1 levels and enzymatic activities and amyloid- peptide levels.
Results Increased CSF levels of BACE1 protein were associated with increased risk ratios (RRs) for patients with MCI compared with controls (RR, 2.08; 95% confidence interval [CI], 1.58-2.58) and patients with AD (RR, 1.65; 95% CI, 1.19-2.03). Similarly, patients with MCI showed increased levels of BACE1 activity compared with controls (RR, 2.17; 95% CI, 1.66-2.71) and patients with AD (RR, 3.71; 95% CI, 2.74-4.36). For total amyloid- peptide and tau, increased CSF levels were associated with a higher risk of MCI compared with controls. The BACE1 activity was significantly correlated with BACE1 protein level (
= 0.23; P<.001) and amyloid- peptide level ( = 0.39; P<.001), with amyloid- peptide correlated with BACE1 protein level ( = 0.30; P<.001).
Conclusion Significant elevation of BACE1 levels and activity in CSF is an indicator of MCI, which could be an early stage of AD.
Author Affiliations: Haldeman Laboratory of Molecular and Cellular Neurobiology, Sun Health Research Institute, Sun City, Ariz (Mr Zhong, Drs He and Shen, and Ms McAllister); Alzheimer Memorial Center, Ludwig-Maximilian University, Munich, Germany (Drs Ewers, Teipel, Bürger, and Hampel); and Department of Clinical Neuroscience, University of Göteborg, Sahlgren's University Hospital, Möndal, Sweden (Drs Wallin and Blennow).
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