Department of Gerontology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Department of Radiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
CNS Neurosci Ther. 2022 Dec;28(12):2195-2205. doi: 10.1111/cns.13962. Epub 2022 Sep 8.
There is increasing evidence that plasma biomarkers are specific biomarkers for Alzheimer's disease (AD) pathology, but their potential utility in Obj-SCD (objectively defined subtle cognitive decline) remains unclear.
A total of 234 subjects, including 65 with brain amyloid beta (Aβ) negative normal cognition (Aβ- NC), 58 with Aβ-positive NC (Aβ+ NC), 63 with Aβ- Obj-SCD, and 48 with Aβ+ Obj-SCD were enrolled. Plasma Aβ42, Aβ40, Aβ42/Aβ40 ratio, phosphorylated tau181 (p-tau181), neurofilament light chain (NfL), and total tau (T-tau) were measured using Simoa assays. Logistic and linear regression analyses were used to examine the relationship between plasma biomarkers and brain amyloid, cognition, and imaging measures adjusting for age, sex, education, APOE ε4 status, and vascular risk scores. Receiver operating characteristics were used to evaluate the discriminative validity of biomarkers.
After adjustment, only plasma p-tau181 and NfL were significantly elevated in Aβ+ Obj-SCD participants compared to Aβ- NC group. Elevated p-tau181 was associated with brain amyloid accumulation, worse cognitive performance (visual episodic memory, executive function, and visuospatial function), and hippocampal atrophy. These associations mainly occurred in Aβ+ individuals. In contrast, higher NfL was correlated with brain amyloid burden and verbal memory decline. These associations predominantly occurred in Aβ- individuals. The adjusted diagnostic model combining p-tau181 and NfL levels showed the best performance in identifying Aβ+ Obj-SCD from Aβ- NC [area under the curve (AUC) = 0.814], which did not differ from the adjusted p-tau181 model (AUC = 0.763).
Our findings highlight that plasma p-tau181, alone or combined with NfL, contributes to identifying high-risk AD populations.
越来越多的证据表明，血浆生物标志物是阿尔茨海默病（AD）病理的特异性生物标志物，但它们在Obj-SCD（客观定义的轻度认知障碍）中的潜在效用尚不清楚。
共纳入 234 名受试者，包括 65 名脑淀粉样蛋白β（Aβ）阴性正常认知（Aβ-NC）者、58 名 Aβ 阳性 NC（Aβ+NC）者、63 名 Aβ-NC Obj-SCD 者和 48 名 Aβ+Obj-SCD 者。使用 Simoa 检测法测量血浆 Aβ42、Aβ40、Aβ42/Aβ40 比值、磷酸化 tau181（p-tau181）、神经丝轻链（NfL）和总 tau（T-tau）。使用逻辑和线性回归分析，在调整年龄、性别、教育、APOE ε4 状态和血管风险评分后，检查血浆生物标志物与脑淀粉样蛋白、认知和影像学测量值之间的关系。使用受试者工作特征曲线评估生物标志物的判别有效性。
调整后，与 Aβ-NC 组相比，仅 Aβ+Obj-SCD 参与者的血浆 p-tau181 和 NfL 显著升高。升高的 p-tau181 与脑淀粉样蛋白积聚、认知表现（视觉情景记忆、执行功能和视空间功能）下降以及海马萎缩有关。这些关联主要发生在 Aβ+个体中。相比之下，更高的 NfL 与脑淀粉样蛋白负担和言语记忆下降相关。这些关联主要发生在 Aβ-个体中。结合 p-tau181 和 NfL 水平的调整后诊断模型在从 Aβ-NC 中识别 Aβ+Obj-SCD 方面表现最佳[曲线下面积（AUC）=0.814]，与调整后的 p-tau181 模型（AUC=0.763）无差异。
我们的研究结果强调，血浆 p-tau181 单独或与 NfL 联合使用有助于识别 AD 高危人群。
