Apolipoproteins C-I, C-II and C-III interact with ApoE to regulate lipoprotein metabolism and contribute to Alzheimer's disease pathophysiology. In plasma, apoC-I and C-II exist as truncated isoforms, while apoC-III exhibits multiple glycoforms. This study aimed to 1. delineate apoC-I, C-II and C-III isoform profiles in CSF and plasma in a cohort of non-demented older individuals (n = 61), and 2. examine the effect of APOE4 on these isoforms and their correlation with CSF Aβ42, a surrogate of brain amyloid accumulation. The isoforms of the apoCs were immunoaffinity enriched and measured with MALDI-TOF mass spectrometry, revealing a significantly higher percentage of truncated apoC-I and apoC-II in CSF compared to matched plasma, with positive correlation between CSF and plasma. A greater percentage of monosialylated and disialylated apoC-III isoforms was detected in CSF, accompanied by a lower percentage of the two non-sialylated apoC-III isoforms, with significant linear correlations between CSF and plasma. Furthermore, a greater percentage of truncated apoC-I in CSF, and apoC-II in plasma and CSF, was observed in individuals carrying at least one apoE Ɛ4 allele. Increased apoC-I and apoC-II truncations were associated with lower CSF Aβ42. Finally, monosialylated apoC-III was lower, and disialylated apoC-III greater in the CSF of Ɛ4 carriers. Together, these results reveal distinct patterns of the apoCs isoforms in CSF, implying CSF-specific apoCs processing. These patterns were accentuated in APOE Ɛ4 allele carriers, suggesting an association between APOE4 genotype and Alzheimer's disease pathology with apoCs processing and function in the brain.

中文翻译：

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载脂蛋白 CI、C-II 和 C-III 亚型的不同模式与阿尔茨海默病的标志物相关。

载脂蛋白 CI、C-II 和 C-III 与 ApoE 相互作用，调节脂蛋白代谢并促进阿尔茨海默病的病理生理学。在血浆中，apoC-I 和 C-II 以截短的亚型存在，而 apoC-III 则呈现多种糖型。本研究旨在 1. 描绘一组非痴呆老年人 (n = 61) 的脑脊液和血浆中的 apoC-I、C-II 和 C-III 同工型谱，以及 2. 检查 APOE4 对这些同工型的影响及其与 CSF Aβ42（大脑淀粉样蛋白积累的替代物）的相关性。通过 MALDI-TOF 质谱法对 apoC 亚型进行免疫亲和富集和测量，结果显示，与匹配血浆相比，CSF 中截短的 apoC-I 和 apoC-II 的百分比显着更高，并且 CSF 和血浆之间呈正相关。在 CSF 中检测到较高百分比的单唾液酸化和二唾液酸化 apoC-III 亚型，同时检测到两种非唾液酸化 apoC-III 亚型的百分比较低，且 CSF 和血浆之间存在显着的线性相关性。此外，在携带至少一个 apoE Ɛ4 等位基因的个体中，观察到脑脊液中截短的 apoC-I 以及血浆和脑脊液中 apoC-II 的比例较高。apoC-I 和 apoC-II 截断增加与 CSF Aβ42 降低相关。最后，Ɛ4 携带者的 CSF 中单唾液酸化 apoC-III 较低，二唾液酸化 apoC-III 较高。总之，这些结果揭示了 CSF 中 apoC 亚型的不同模式，这意味着 CSF 特异性 apoC 加工。这些模式在 APOE Ɛ4 等位基因携带者中得到强调，