Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA.
Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA; Department of Neurology, Peking University Third Hospital, Beijing, China.
Alzheimers Dement. 2018 Aug;14(8):1052-1062. doi: 10.1016/j.jalz.2018.02.015. Epub 2018 Mar 28.
The ability of Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers (amyloid β peptide 1-42, total tau, and phosphorylated tau) to discriminate AD from related disorders is limited. Biomarkers for other concomitant pathologies (e.g., CSF α-synuclein [α-syn] for Lewy body pathology) may be needed to further improve the differential diagnosis.
CSF total α-syn, phosphorylated α-syn at Ser129, and AD CSF biomarkers were evaluated with Luminex immunoassays in 367 participants, followed by validation in 74 different neuropathologically confirmed cases.
CSF total α-syn, when combined with amyloid β peptide 1-42 and either total tau or phosphorylated tau, improved the differential diagnosis of AD versus frontotemporal dementia, Lewy body disorders, or other neurological disorders. The diagnostic accuracy of the combined models attained clinical relevance (area under curve ∼0.9) and was largely validated in neuropathologically confirmed cases.
Combining CSF biomarkers representing AD and Lewy body pathologies may have clinical value in the differential diagnosis of AD.
阿尔茨海默病(AD)脑脊液(CSF)生物标志物(β淀粉样蛋白 1-42、总 tau 和磷酸化 tau)区分 AD 与相关疾病的能力有限。可能需要其他伴随病理的生物标志物(例如,路易体病理的 CSF α-突触核蛋白 [α-syn])来进一步改善鉴别诊断。
采用 Luminex 免疫分析法检测 367 名参与者的 CSF 总 α-syn、磷酸化 α-syn 第 129 位丝氨酸和 AD CSF 生物标志物,随后在 74 例不同神经病理学确诊病例中进行验证。
当 CSF 总 α-syn 与β淀粉样蛋白 1-42 以及总 tau 或磷酸化 tau 联合使用时,可以改善 AD 与额颞叶痴呆、路易体障碍或其他神经疾病的鉴别诊断。组合模型的诊断准确性达到了临床相关性(曲线下面积约为 0.9),并在神经病理学确诊病例中得到了广泛验证。
联合 AD 和路易体病理的 CSF 生物标志物可能在 AD 的鉴别诊断中具有临床价值。