During the last two decades, neuropathological examination of the brain has evolved both technically and scientifically. The increasing use of immunohistochemistry to detect protein aggregates paralleled a better understanding of neuroanatomical progression of protein deposition. As a consequence, an international effort was achieved to standardize hyperphosphorylated-Tau (phospho-TAU), ßAmyloid (Aß), alpha syncuclein (alpha-syn), phosphorylated transactive response DNA-binding protein 43 (phospho-TDP43) and vascular pathology detection. Meanwhile harmonized staging systems emerged in order to increase inter rater reproducibility. Therefore, a refined definition of Alzheimer's disease was recommended., a clearer picture of the neuropathological lesions diversity emerged secondarily to the systematic assessment of concomitant pathology highlighting finally a low rate of pure AD pathology. This brings new challenges to laboratory medicine in the field of cerebrospinal fluid (CSF) markers of Alzheimer's disease: how to further validate total Tau, phospho-TAU, Aß40 and Aß42 and new marker level cut-offs while autopsy rates are declining?

中文翻译：

---

脑脊液标记物和神经病理学诊断的标准化揭示了阿尔茨海默氏病伴随的病理学的频繁复杂性：生化标记物的下一个挑战？

在过去的二十年中，大脑的神经病理学检查在技术和科学上都得到了发展。越来越多地使用免疫组织化学来检测蛋白质聚集体，这与对蛋白质沉积的神经解剖学进展有了更好的了解。结果，国际上为标准化高磷酸化Tau（phospho-TAU），ß淀粉样蛋白（Aß），αucuclelein（alpha-syn），磷酸化的交易反应DNA结合蛋白43（phospho-TDP43）进行了标准化，并进行了血管病理学检测。同时，出现了统一的分级系统，以提高评估者之间的可重复性。因此，建议对阿尔茨海默氏病进行精确定义。其次，对伴随病理学的系统评估显示出更清晰的神经病理学病变多样性图景，从而最终突出了纯AD病理学的低发生率。这给阿尔茨海默氏病脑脊髓液（CSF）标记领域的实验室医学带来了新挑战：如何在尸检率下降的同时进一步验证总Tau，磷酸TAU，Aß40和Aß42以及新的标记水平截止值？