Center for Imaging of Neurodegenerative Diseases, Department of Veterans Affairs Medical Center, San Francisco, CA 94121, United States.
Neurobiol Aging. 2010 Aug;31(8):1340-54. doi: 10.1016/j.neurobiolaging.2010.04.030. Epub 2010 Jun 8.
Previously it was reported that Alzheimer's disease (AD) patients have reduced beta amyloid (Abeta(1-42)) and elevated total tau (t-tau) and phosphorylated tau (p-tau(181p)) in the cerebrospinal fluid (CSF), suggesting that these same measures could be used to detect early AD pathology in healthy elderly individuals and those with mild cognitive impairment (MCI). In this study, we tested the hypothesis that there would be an association among rates of regional brain atrophy, the CSF biomarkers Abeta(1-42), t-tau, and p-tau(181p) and apolipoprotein E (ApoE) epsilon4 status, and that the pattern of this association would be diagnosis-specific. Our findings primarily showed that lower CSF Abeta(1-42) and higher tau concentrations were associated with increased rates of regional brain tissue loss and the patterns varied across the clinical groups. Taken together, these findings demonstrate that CSF biomarker concentrations are associated with the characteristic patterns of structural brain changes in healthy elderly and mild cognitive impairment subjects that resemble to a large extent the pathology seen in AD. Therefore, the finding of faster progression of brain atrophy in the presence of lower Abeta(1-42) levels and higher tau levels supports the hypothesis that CSF Abeta(1-42) and tau are measures of early AD pathology. Moreover, the relationship among CSF biomarkers, ApoE epsilon4 status, and brain atrophy rates are regionally varying, supporting the view that the genetic predisposition of the brain to beta amyloid and tau mediated pathology is regional and disease stage specific.
先前有报道称，阿尔茨海默病（AD）患者的脑脊液（CSF）中β淀粉样蛋白（Abeta(1-42)）减少，总tau（t-tau）和磷酸化 tau（p-tau(181p)）升高，这表明这些相同的指标可用于检测健康老年人和轻度认知障碍（MCI）患者的早期 AD 病理。在这项研究中，我们检验了以下假设：即区域性脑萎缩的速度、CSF 生物标志物 Abeta(1-42)、t-tau 和 p-tau(181p)以及载脂蛋白 E (ApoE) epsilon4 状态之间存在关联，并且这种关联的模式具有诊断特异性。我们的研究结果主要表明，CSF Abeta(1-42)水平降低和 tau 浓度升高与区域性脑组织丢失的速度增加相关，且这种关联模式在不同的临床组中有所不同。总的来说，这些发现表明 CSF 生物标志物浓度与健康老年人和轻度认知障碍受试者的结构性脑变化特征模式相关，在很大程度上类似于 AD 中的病理变化。因此，在 Abeta(1-42)水平降低和 tau 水平升高的情况下，脑萎缩速度更快的发现支持 CSF Abeta(1-42)和 tau 是 AD 早期病理的指标的假设。此外，CSF 生物标志物、ApoE epsilon4 状态和脑萎缩速度之间的关系在区域上存在差异，这支持了脑对β淀粉样蛋白和 tau 介导的病理的遗传易感性具有区域性和疾病阶段特异性的观点。
