Research and Development, Novartis Vaccines and Diagnostics, Emeryville, California, United States of America.
PLoS One. 2010 Dec 30;5(12):e15725. doi: 10.1371/journal.pone.0015725.
Alzheimer's Disease (AD) is the most prevalent form of dementia worldwide, yet the development of therapeutics has been hampered by the absence of suitable biomarkers to diagnose the disease in its early stages prior to the formation of amyloid plaques and the occurrence of irreversible neuronal damage. Since oligomeric Aβ species have been implicated in the pathophysiology of AD, we reasoned that they may correlate with the onset of disease. As such, we have developed a novel misfolded protein assay for the detection of soluble oligomers composed of Aβ x-40 and x-42 peptide (hereafter Aβ40 and Aβ42) from cerebrospinal fluid (CSF). Preliminary validation of this assay with 36 clinical samples demonstrated the presence of aggregated Aβ40 in the CSF of AD patients. Together with measurements of total Aβ42, diagnostic sensitivity and specificity greater than 95% and 90%, respectively, were achieved. Although larger sample populations will be needed to confirm this diagnostic sensitivity, our studies demonstrate a sensitive method of detecting circulating Aβ40 oligomers from AD CSF and suggest that these oligomers could be a powerful new biomarker for the early detection of AD.
阿尔茨海默病（AD）是全球最常见的痴呆症形式，但由于缺乏合适的生物标志物，无法在淀粉样斑块形成和不可逆神经元损伤发生之前早期诊断该病，因此治疗药物的研发一直受到阻碍。由于寡聚体 Aβ 已被认为与 AD 的病理生理学有关，我们推断它们可能与疾病的发作有关。因此，我们开发了一种新的错误折叠蛋白检测方法，用于检测来自脑脊液（CSF）的 Aβ x-40 和 x-42 肽（以下简称 Aβ40 和 Aβ42）组成的可溶性寡聚体。用 36 个临床样本对该检测方法进行的初步验证表明，AD 患者的 CSF 中存在聚集的 Aβ40。与总 Aβ42 的测量结果相结合，分别实现了大于 95%和 90%的诊断灵敏度和特异性。尽管需要更大的样本群体来确认这种诊断灵敏度，但我们的研究表明了一种从 AD CSF 中检测循环 Aβ40 寡聚体的敏感方法，并表明这些寡聚体可能成为 AD 早期检测的有力新生物标志物。
