Blennow Kaj
Department of Clinical Neuroscience, Section of Experimental Neuroscience, The Sahlgrenska Academy at Göteborg University, SE-43180 Göteborg, Sweden.
NeuroRx. 2004 Apr;1(2):213-25. doi: 10.1602/neurorx.1.2.213.
The introduction of acetylcholine esterase (AChE) inhibitors as a symptomatic treatment of Alzheimer's disease (AD) has made patients seek medical advice at an earlier stage of the disease. This has highlighted the importance of diagnostic markers for early AD. However, there is no clinical method to determine which of the patients with mild cognitive impairment (MCI) will progress to AD with dementia, and which have a benign form of MCI without progression. In this paper, the performance of cerebrospinal fluid (CSF) protein biomarkers for AD is reviewed. The diagnostic performance of the three biomarkers, total tau, phospho-tau, and the 42 amino acid form of beta-amyloid have been evaluated in numerous studies and their ability to identify incipient AD in MCI cases has also been studied. Some candidate AD biomarkers including ubiquitin, neurofilament proteins, growth-associated protein 43 (neuromodulin), and neuronal thread protein (AD7c) show interesting results but have been less extensively studied. It is concluded that CSF biomarkers may have clinical utility in the differentiation between AD and several important differential diagnoses, including normal aging, depression, alcohol dementia, and Parkinson's disease, and also in the identification of Creutzfeldt-Jakob disease in cases with rapidly progressive dementia. Early diagnosis of AD is not only of importance to be able to initiate symptomatic treatment with AChE inhibitors, but will be the basis for initiation of treatment with drugs aimed at slowing down or arresting the degenerative process, such as gamma-secretase inhibitors, if these prove to affect AD pathology and to have a clinical effect.
乙酰胆碱酯酶（AChE）抑制剂作为阿尔茨海默病（AD）的对症治疗药物的引入，使得患者在疾病的早期阶段就寻求医疗建议。这凸显了早期AD诊断标志物的重要性。然而，目前尚无临床方法来确定哪些轻度认知障碍（MCI）患者会进展为伴有痴呆的AD，哪些是不会进展的良性MCI形式。本文综述了脑脊液（CSF）蛋白质生物标志物对AD的诊断性能。在众多研究中评估了三种生物标志物——总tau蛋白、磷酸化tau蛋白和β淀粉样蛋白42氨基酸形式的诊断性能，并且也研究了它们在识别MCI病例中早期AD的能力。一些候选AD生物标志物，包括泛素、神经丝蛋白、生长相关蛋白43（神经调节蛋白）和神经元纤维蛋白（AD7c）显示出有趣的结果，但研究较少。结论是，CSF生物标志物在AD与几种重要鉴别诊断（包括正常衰老、抑郁症、酒精性痴呆和帕金森病）的区分中可能具有临床应用价值，并且在快速进展性痴呆病例中识别克雅氏病方面也有应用价值。AD的早期诊断不仅对于能够启动AChE抑制剂的对症治疗很重要，而且如果事实证明某些药物（如γ-分泌酶抑制剂）能够影响AD病理并产生临床效果，那么早期诊断将成为启动旨在减缓或阻止退行性过程的药物治疗的基础。
