Department of Geriatric Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University of Medicine, Shanghai, China.
Department of Geriatric Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University of Medicine, Shanghai, China.
Exp Gerontol. 2024 Oct 1;195:112535. doi: 10.1016/j.exger.2024.112535. Epub 2024 Aug 15.
Glial fibrillary acidic protein (GFAP) and neurofilament light (NfL) are putative non-amyloid biomarkers indicative of ongoing inflammatory and neurodegenerative disease processes. Hence, this study aimed to demonstrate the relationship between plasma biomarkers (GFAP and NfL) and F-AV-1451 tau PET images, and to explore their effects on cognitive function. Ninety-one participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database and 20 participants from the Shanghai Action of Prevention Dementia for the Elderly (SHAPE) cohort underwent plasma biomarker testing, F-AV-1451 tau PET scans and cognitive function assessments. Within the ADNI, there were 42 cognitively normal (CN) individuals and 49 with mild cognitive impairment (MCI). Similarly, in the SHAPE, we had 10 CN and 10 MCI participants. We calculated the standardized uptake value ratios (SUVRs) for the regions of interest (ROIs) in the F-AV-1451 PET scans. Using plasma biomarkers and regional SUVRs, we trained machine learning models to differentiate between MCI and CN subjects with ADNI database and validated in SHAPE. Results showed that eight selected variables (including left amygdala SUVR, right amygdala SUVR, left entorhinal cortex SUVR, age, education, plasma NfL, plasma GFAP, plasma GFAP/ NfL) identified by LASSO could differentiate between the MCI and CN individuals, with AUC ranging from 0.783 to 0.926. Additionally, cognitive function was negatively associated with the plasma biomarkers and tau deposition in amygdala and left entorhinal cortex. Increased tau deposition in amygdala and left entorhinal cortex were related to increased plasma biomarkers. Moreover, tau pathology mediated the effect of plasma biomarkers level on the cognitive decline. The present study provides valuable insights into the association among plasma markers (GFAP and NfL), regional tau deposition and cognitive function. This study reports the mediation effect of brain regions tau deposition on the plasma biomarkers level and cognitive function, indicating the significance of tau pathology in the MCI patients.
胶质纤维酸性蛋白（GFAP）和神经丝轻链（NfL）是潜在的非淀粉样生物标志物，提示存在持续的炎症和神经退行性疾病过程。因此，本研究旨在证明血浆生物标志物（GFAP 和 NfL）与 F-AV-1451 tau PET 图像之间的关系，并探讨它们对认知功能的影响。来自阿尔茨海默病神经影像学倡议（ADNI）数据库的 91 名参与者和来自上海预防老年痴呆症行动（SHAPE）队列的 20 名参与者接受了血浆生物标志物检测、F-AV-1451 tau PET 扫描和认知功能评估。在 ADNI 中，有 42 名认知正常（CN）个体和 49 名轻度认知障碍（MCI）个体。同样，在 SHAPE 中，我们有 10 名 CN 和 10 名 MCI 参与者。我们计算了 F-AV-1451 PET 扫描中感兴趣区域（ROI）的标准化摄取值比（SUVR）。使用血浆生物标志物和 ROI 的 SUVR，我们使用 ADNI 数据库训练机器学习模型来区分 MCI 和 CN 受试者，并在 SHAPE 中进行验证。结果表明，LASSO 选择的 8 个变量（包括左杏仁核 SUVR、右杏仁核 SUVR、左内嗅皮质 SUVR、年龄、教育、血浆 NfL、血浆 GFAP、血浆 GFAP/NfL）可以区分 MCI 和 CN 个体，AUC 范围为 0.783 至 0.926。此外，认知功能与血浆生物标志物和杏仁核及左内嗅皮质的 tau 沉积呈负相关。杏仁核和左内嗅皮质的 tau 沉积增加与血浆生物标志物增加有关。此外，tau 病理学介导了血浆生物标志物水平对认知下降的影响。本研究提供了关于血浆标志物（GFAP 和 NfL）、区域 tau 沉积和认知功能之间关联的有价值的见解。本研究报告了脑区 tau 沉积对血浆标志物水平和认知功能的中介效应，表明 tau 病理学在 MCI 患者中的重要性。
