Centre of Excellence in Alzheimer's Disease Research and Care, School of Medical and Health Sciences, Edith Cowan University, 270 Joondalup Drive, Joondalup, WA, Australia.
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden.
Cell Mol Life Sci. 2019 May;76(10):1833-1863. doi: 10.1007/s00018-019-03040-5. Epub 2019 Feb 15.
Alzheimer's disease (AD) is a multifactorial age-related brain disease. Numerous pathological events run forth in the brain leading to AD. There is an initial long, dormant phase before the clinical symptoms become evident. There is a need to diagnose the disease at the preclinical stage since therapeutic interventions are most likely to be effective if initiated early. Undoubtedly, the core cerebrospinal fluid (CSF) biomarkers have a good diagnostic accuracy and have been used in clinical trials as end point measures. However, looking into the multifactorial nature of AD and the overlapping pathology with other forms of dementia, it is important to integrate the core CSF biomarkers with a broader panel of other biomarkers reflecting different aspects of pathology. The review is focused upon a panel of biomarkers that relate to different aspects of AD pathology, as well as various studies that have evaluated their diagnostic potential. The panel includes markers of neurodegeneration: neurofilament light chain and visinin-like protein (VILIP-1); markers of amyloidogenesis and brain amyloidosis: apolipoproteins; markers of inflammation: YKL-40 and monocyte chemoattractant protein 1; marker of synaptic dysfunction: neurogranin. These markers can highlight on the state and stage-associated changes that occur in AD brain with disease progression. A combination of these biomarkers would not only aid in preclinical diagnosis, but would also help in identifying early brain changes during the onset of disease. Successful treatment strategies can be devised by understanding the contribution of these markers in different aspects of disease pathogenesis.
阿尔茨海默病（AD）是一种与年龄相关的多因素脑疾病。大量的病理事件在大脑中发生，导致 AD。在临床症状明显之前，有一个初始的漫长潜伏期。有必要在临床前阶段诊断这种疾病，因为如果早期开始治疗，干预措施很可能更有效。毫无疑问，核心脑脊液（CSF）生物标志物具有良好的诊断准确性，并已在临床试验中用作终点测量。然而，鉴于 AD 的多因素性质以及与其他形式痴呆症的重叠病理学，将核心 CSF 生物标志物与更广泛的其他标志物面板相结合，以反映病理学的不同方面非常重要。该综述重点介绍了一组与 AD 病理学不同方面相关的生物标志物，以及评估其诊断潜力的各种研究。该小组包括神经退行性变标志物：神经丝轻链和视黄醇结合蛋白 1（VILIP-1）；淀粉样形成和脑淀粉样变标志物：载脂蛋白；炎症标志物：YKL-40 和单核细胞趋化蛋白 1；突触功能障碍标志物：神经颗粒蛋白。这些标志物可以突出 AD 大脑在疾病进展过程中发生的与状态和阶段相关的变化。这些生物标志物的组合不仅有助于临床前诊断，还有助于在疾病发作时识别早期脑变化。通过了解这些标志物在疾病发病机制的不同方面的贡献，可以制定成功的治疗策略。
