Thapa Simrika, Anastassiadis Chloe, Vasilevskaya Anna, Taghdiri Foad, Jurisica Igor, Hadian Mohsen, Salwierz Patrick, Robbani Faiza, Kivisäkk Pia, Hyman Bradley, Arnold Steven E, Ingelsson Martin, Haas Wilhelm, Lozano Andres M, Tang-Wai David F, Tartaglia Maria Carmela
Tanz Centre for Research on Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada.
University Health Network (UHN) Memory Clinic, Krembil Brain Institute, Toronto, Ontario, Canada.
Alzheimers Dement. 2025 Jul;21(7):e70509. doi: 10.1002/alz.70509.
Neuroinflammation, a key player in Alzheimer's disease (AD) pathogenesis, may be differentially involved in young-onset (YOAD) compared to late-onset (LOAD) AD.
Using proximity extension assay technology, we examined 737 inflammatory markers in the CSF of 26 healthy controls (63.9 ± 8.7; 12♀), 57 patients with YOAD (60.8 ± 4.9 y/o; 40♀), and 33 with LOAD (76.6 ± 4.5 y/o; 18♀). We also assessed biomarkers of AD pathology (Aβ42, p-tau181, t-tau) and neurodegeneration (neurofilament light-chain [NfL]).
Compared to controls, SCRN1 and MMP10 were increased in LOAD and YOAD, but 16 markers showed YOAD-specific increases. Forty-six markers were significantly associated with NfL. P-tau181 and t-tau mediated the association between inflammatory markers and NfL in YOAD. In LOAD we could not identify a direct or indirect relationship between neuroinflammation and neurodegeneration.
Using a proteomics approach, we observed an exacerbation of neuroinflammatory changes and a differential contribution of neuroinflammation to AD pathology and neurodegeneration in YOAD compared to LOAD.
Olink's Proximity Extension Assay was used to compare the inflammatory profile of 26 healthy controls and 90 Alzheimer's disease (AD) patients. AD patients were further stratified into young-onset (YOAD, n = 57) and late-onset (LOAD, n = 33) AD. Cerebrospinal fluid (CSF) levels of MMP10 and SCRN1 were increased in both YOAD and LOAD, but 16 proteins were only increased in YOAD. Tau mediated the association between inflammatory markers and neurodegeneration in YOAD. Neuroinflammation may be differentially involved in the pathogenesis of YOAD compared to LOAD.
神经炎症是阿尔茨海默病（AD）发病机制中的关键因素，与晚发型（LOAD）AD相比，其在早发型（YOAD）AD中的作用可能存在差异。
我们采用邻位延伸分析技术，检测了26名健康对照者（63.9±8.7岁；12名女性）、57例早发型AD患者（60.8±4.9岁；40名女性）和33例晚发型AD患者（76.6±4.5岁；18名女性）脑脊液中的737种炎症标志物。我们还评估了AD病理生物标志物（Aβ42、p-tau181、t-tau）和神经退行性变标志物（神经丝轻链[NfL]）。
与对照组相比，SCRN1和MMP10在晚发型和早发型AD中均升高，但有16种标志物仅在早发型AD中特异性升高。46种标志物与NfL显著相关。在早发型AD中，p-tau181和t-tau介导了炎症标志物与NfL之间的关联。在晚发型AD中，我们未发现神经炎症与神经退行性变之间存在直接或间接关系。
通过蛋白质组学方法，我们观察到与晚发型AD相比，早发型AD中神经炎症变化加剧，且神经炎症对AD病理和神经退行性变的贡献存在差异。
使用Olink邻位延伸分析比较26名健康对照者和90例阿尔茨海默病（AD）患者的炎症谱。AD患者进一步分为早发型（YOAD，n = 57）和晚发型（LOAD，n = 33）AD。早发型和晚发型AD患者脑脊液中MMP10和SCRN1水平均升高，但有16种蛋白质仅在早发型AD中升高。Tau介导了早发型AD中炎症标志物与神经退行性变之间的关联。与晚发型AD相比，神经炎症可能在早发型AD发病机制中发挥不同作用。
