Weill Medical College of Cornell University, New York, NY, USA.
Prog Neurobiol. 2011 Dec;95(4):601-13. doi: 10.1016/j.pneurobio.2011.09.002. Epub 2011 Sep 19.
Parkinson's disease (PD) and Dementia with Lewy bodies (DLB) are progressive and disabling neurodegenerative disorders, in which signs and symptoms overlap with each other and with other neurodegenerative conditions. Currently, diagnosis, measurement of progression, and response to therapeutic intervention rely upon clinical observation. However, there remains a critical need for validated biomarkers in each of these areas. A definitive diagnostic test would improve clinical management and enrollment into clinical trials. An objective measure of progression is vitally important in identifying neuroprotective interventions. Biomarkers may also provide insight into pathogenesis, and might therefore suggest possible novel targets for therapeutic intervention. In addition, certain biomarkers might be of use in monitoring the biochemical and physiological effects of therapeutic interventions. Development of diagnostic biomarkers has focused until recently upon imaging techniques based upon measuring loss of dopamine neurons. Additionally, advances in understanding the genetic contribution to neurodegenerative disorders, in particular in PD, have identified multiple causative genes and risk factors that in some cases may help estimate PD risk. However, recent availability of increasingly sophisticated bioinformatics technology has rendered development of fluid biomarkers feasible, opening the possibility of generally accessible blood or cerebrospinal fluid (CSF) tests that could impact upon diagnosis, management, and research in PD, PDD, and DLB.
帕金森病 (PD) 和路易体痴呆 (DLB) 是进行性和致残性神经退行性疾病,其症状和体征相互重叠,也与其他神经退行性疾病重叠。目前,诊断、进展测量和治疗干预反应依赖于临床观察。然而,在这些领域都迫切需要经过验证的生物标志物。明确的诊断测试将改善临床管理并有助于临床试验的招募。客观的进展衡量标准对于识别神经保护干预措施至关重要。生物标志物还可以深入了解发病机制,因此可能为治疗干预提供新的潜在靶点。此外,某些生物标志物可能有助于监测治疗干预的生化和生理影响。诊断生物标志物的开发直到最近才集中在基于测量多巴胺神经元损失的成像技术上。此外,对神经退行性疾病遗传贡献的理解的进步,特别是在 PD 中,已经确定了多个致病基因和风险因素,在某些情况下,这些因素可能有助于估计 PD 的风险。然而,最近越来越复杂的生物信息学技术的出现使得开发液体生物标志物成为可能,这为血液或脑脊液 (CSF) 测试提供了普遍可行的机会,这些测试可能会影响 PD、PDD 和 DLB 的诊断、管理和研究。