Laboratory of Neuroscience, International Center for Biomedicine (ICC) and Faculty of Sciences, University of Chile, Santiago, Chile.
Department of Neurology, Faculty of Medicine, University of Chile, Santiago, Chile.
J Alzheimers Dis. 2019;67(4):1181-1186. doi: 10.3233/JAD-180637.
The establishment of a molecular biomarker for early detection of Alzheimer's disease (AD) is critical for diagnosis and follow up of patients, and as a quantitative parameter in the evaluation of potential new drugs to control AD. A list of blood biomarkers has been reported but none has been validated for the Alzheimer's clinic. The changes in hyperphosphorylated tau and amyloid peptide in the cerebrospinal fluid is currently used as a tool in the clinics and for research purposes, but this method is highly invasive. Recently, we reported a non-invasive and reliable blood biomarker that correlates the increase in the ratio of heavy tau (HMWtau) and the low molecular weight tau (LMWtau) in human platelets and the decrease in the brain volume as measured by structural MRI. This molecular marker has been named Alz-tau®. Beyond the clinical trials developed with a Latin American population, the present study focuses on an evaluation of this biomarker in a Caucasian population. We examined 36 AD patients and 15 cognitively normal subjects recruited in Barcelona, Spain. Tau levels in platelets were determined by immunoreactivity and the cognitive status by using GDS and MMSE neuropsychological tests. The HMW/LMW tau ratio was statistically different between controls and AD patients. A high correlation was found between the increase in MMSE scores and HMW/LMW tau ratio. This study showed that this ratio is significantly higher in AD patients than controls. Moreover, this study on a peripheral marker of AD is valuable to understanding the AD pathogenesis.
建立用于阿尔茨海默病（AD）早期检测的分子生物标志物对于诊断和随访患者非常重要，并且是评估潜在治疗 AD 新药的定量参数。已经报道了一系列血液生物标志物，但没有一种在阿尔茨海默氏症临床中得到验证。脑脊液中过度磷酸化的 tau 和淀粉样肽的变化目前在临床上和研究中用作工具，但这种方法具有高度侵入性。最近，我们报道了一种非侵入性和可靠的血液生物标志物，该标志物与人血小板中重 tau（HMWtau）和低分子量 tau（LMWtau）的比率增加以及结构 MRI 测量的脑体积减少相关。这种分子标志物被命名为 Alz-tau®。除了在拉丁美洲人群中进行临床试验外，本研究还重点评估了该生物标志物在白种人群中的应用。我们检查了 36 名 AD 患者和 15 名认知正常的受试者，他们来自西班牙巴塞罗那。通过免疫反应测定血小板中的 tau 水平，并通过 GDS 和 MMSE 神经心理学测试评估认知状态。对照组和 AD 患者之间 HMW/LMW tau 比率存在统计学差异。发现 MMSE 评分的增加与 HMW/LMW tau 比率之间存在高度相关性。这项研究表明，AD 患者的 HMW/LMW tau 比率明显高于对照组。此外，这项针对 AD 外周标志物的研究对于了解 AD 的发病机制具有重要价值。
