Sancesario Giulia M, Bernardini Sergio
IRCCS Santa Lucia Foundation, Department of Clinical and Behavioural Neurology, Rome, Italy.
Department of Experimental Medicine, Tor Vergata University General Hospital, Rome, Italy.
Ann Transl Med. 2018 Sep;6(17):340. doi: 10.21037/atm.2018.08.04.
After many years of large efforts made for understanding the pathogenesis of dementias, the early diagnosis of these degenerative diseases remains an open challenge. Alzheimer's disease (AD) represents the most common form of dementia, followed by Lewy body disease and frontotemporal degeneration. Actually, different pathological processes can determine similar and overlapping clinical syndrome. To detect the pathological process underlying progressive cognitive and behavior impairment, the Internationals guidelines recommend the use of biological and topographical markers, which can reflect neuropathological modifications in brain. In cerebrospinal fluid (CSF), decrease of amyloid beta 1-42 (Aβ42) and a low ratio of Aβ42 with amyloid beta 1-40 (Aβ42/Aβ40), together with the increase of both total tau protein (t-tau) and phosphorylated tau (p-tau), contribute to define the "Alzheimer's signature". This review points out on the evolution of the concept for early diagnosis of AD, and on the current use of CSF proteins for research purposes and in clinical setting. Then, we discuss the limitations and drawbacks in wide application of CSF biomarkers for diagnosing degenerative dementias, and on the role of laboratory medicine to convey these biomarkers from "research" toward "clinical practice".
在为理解痴呆症的发病机制付出多年巨大努力之后，这些退行性疾病的早期诊断仍然是一个悬而未决的挑战。阿尔茨海默病（AD）是最常见的痴呆形式，其次是路易体病和额颞叶变性。实际上，不同的病理过程可导致相似且重叠的临床综合征。为了检测进行性认知和行为障碍背后的病理过程，国际指南建议使用能够反映大脑神经病理改变的生物学和影像学标志物。在脑脊液（CSF）中，淀粉样蛋白β1-42（Aβ42）减少以及Aβ42与淀粉样蛋白β1-40（Aβ42/Aβ40）的比例降低，再加上总tau蛋白（t-tau）和磷酸化tau蛋白（p-tau）均升高，有助于确定“阿尔茨海默特征”。本综述指出了AD早期诊断概念的演变，以及目前CSF蛋白在研究目的和临床环境中的应用情况。然后，我们讨论了CSF生物标志物在诊断退行性痴呆广泛应用中的局限性和缺点，以及检验医学在将这些生物标志物从“研究”转化为“临床实践”中的作用。
