Bailey Peter
Department of Medicine, Dalhousie University, Saint John Regional Hospital, Saint John, New Brunswick, Canada.
Can J Neurol Sci. 2007 Mar;34 Suppl 1:S72-6. doi: 10.1017/s0317167100005618.
Biomarkers are required to improve our diagnostic sensitivity and specificity and to monitor the biological activity of the Alzheimer's disease (AD) in terms of the burden of neural involvement and the tempo of disease progression. Biomarkers will initially supplement our more traditional neuropsychological and imaging markers but may eventually evolve into useful surrogate endpoints in AD research. These markers may also provide important mechanistic clues to the pharmacological action of anti-dementia compounds. At this point, the combination of elevated cerebrospinal fluid phosphorylated TAU (CSF p-TAU) proteins and low CSF ABeta(1-42) are the only biomarkers with the sensitivity and specificity to serve as useful diagnostic biomarkers capable of distinguishing AD from other dementias in the early stages. Advances in non CSF tests is urgently required. Markers assessing the progression of disease do not necessarily require the same high disease specificity as diagnostic markers, but need to be sensitive to changes in disease state. At present, candidate markers fall under four main biological rationales: (1) Specific markers of AD neuropathology; (2) Non-specific markers of neural degeneration; (3) Markers of oxidative stress; (4) Markers of neural inflammation. It is foreseeable that a panel of such markers might prove advantageous. It will be important to develop "non-invasive" markers utilizing readily obtainable tissue samples such as serum or urine to monitor disease progression (or hopefully regression). Repeated sampling would allow for comparison with traditional neuropsychological and imaging measures. The assays themselves will need to be reproducible, reliable and relatively inexpensive. Unfortunately, these biomarkers are in the formative stages of testing and results at present are inconclusive. To facilitate biomarker development in the future it would be highly advantageous to begin to collect and store biological specimens as an adjunct to current research in AD.
需要生物标志物来提高我们的诊断敏感性和特异性，并根据神经受累负担和疾病进展速度来监测阿尔茨海默病（AD）的生物活性。生物标志物最初将补充我们更传统的神经心理学和影像学标志物，但最终可能会演变成AD研究中有用的替代终点。这些标志物还可能为抗痴呆化合物的药理作用提供重要的机制线索。目前，脑脊液磷酸化TAU（CSF p-TAU）蛋白升高和脑脊液β淀粉样蛋白1-42（CSF ABeta(1-42)）降低的组合是仅有的具有敏感性和特异性、能够在早期阶段将AD与其他痴呆症区分开来的有用诊断生物标志物。迫切需要非脑脊液检测方法取得进展。评估疾病进展的标志物不一定需要与诊断标志物相同的高疾病特异性，但需要对疾病状态的变化敏感。目前，候选标志物主要基于四个生物学原理：（1）AD神经病理学的特异性标志物；（2）神经变性的非特异性标志物；（3）氧化应激标志物；（4）神经炎症标志物。可以预见，一组这样的标志物可能会被证明是有利的。利用血清或尿液等易于获取的组织样本开发“非侵入性”标志物以监测疾病进展（或有望实现疾病逆转）将非常重要。重复采样将允许与传统的神经心理学和影像学测量进行比较。检测方法本身需要具有可重复性、可靠性且相对便宜。不幸的是，这些生物标志物正处于测试的形成阶段，目前的结果尚无定论。为了促进未来生物标志物的开发，作为AD当前研究的辅助手段开始收集和存储生物标本将非常有利。
