Plasma transferrin and hemopexin are associated with altered Aβ uptake and cognitive decline in Alzheimer's disease pathology
Plasma transferrin and hemopexin are associated with altered Aβ uptake and cognitive decline in Alzheimer's disease pathology
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DOI：
10.1186/s13195-020-00634-1
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发表时间：
2020-06-09
影响因子：
9
通讯作者：
So, Po-Wah
中科院分区：
文献类型：
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作者：
Ashraf, Azhaar;Ashton, Nicholas J.;So, Po-Wah
研究背景阿尔茨海默病（AD）患者体内血红素和铁稳态受到干扰;因此，该研究的目的是检测来自澳大利亚成像研究所的认知正常（CN）、轻度认知障碍（MCI）和AD个体中血红素与铁结合血浆蛋白的水平和相关性，老龄化的生物标志物和生活方式旗舰研究（Aibl）和克尔圣公会退休村倡议老龄健康（KARVIAH）队列。方法采用高分辨质谱技术对来自Aibl队列的144例CN个体和来自KARVIAH队列的94例CN个体以及来自Aibl队列的21例MCI和25例AD个体的血浆样本进行非靶向蛋白质组学分析。ANCOVA模型用于评估血红素/铁代谢中涉及的血浆蛋白的差异，同时进行多元回归建模（和部分相关性）以检查血红素和铁蛋白、结构神经成像和认知测量之间的关联。结果在参与铁和血红素代谢的血浆蛋白中，AD患者的血红蛋白β亚基（p = 0.001）显著高于CN患者。在Aibl队列中，根据年龄、性别、APOE β 4基因型和疾病状态调整的多元回归模型显示，转铁蛋白水平较低，但血红素结合蛋白水平较高，与脑淀粉样蛋白沉积增加相关。同时，转铁蛋白与海马体积和MMSE表现呈正相关，而血红素结合蛋白与CDR评分呈负相关。偏相关分析显示，缺乏显着的关联血红素/铁蛋白在CN个人进展到认知障碍。结论血红素铁稳态失调是AD的一个特征。血红素/铁代谢与AD之间的因果关系需要进一步研究。
Background Heme and iron homeostasis is perturbed in Alzheimer's disease (AD); therefore, the aim of the study was to examine the levels and association of heme with iron-binding plasma proteins in cognitively normal (CN), mild cognitive impairment (MCI), and AD individuals from the Australian Imaging, Biomarker and Lifestyle Flagship Study of Ageing (AIBL) and Kerr Anglican Retirement Village Initiative in Ageing Health (KARVIAH) cohorts. Methods Non-targeted proteomic analysis by high-resolution mass spectrometry was performed to quantify relative protein abundances in plasma samples from 144 CN individuals from the AIBL and 94 CN from KARVIAH cohorts and 21 MCI and 25 AD from AIBL cohort. ANCOVA models were utilized to assess the differences in plasma proteins implicated in heme/iron metabolism, while multiple regression modeling (and partial correlation) was performed to examine the association between heme and iron proteins, structural neuroimaging, and cognitive measures. Results Of the plasma proteins implicated in iron and heme metabolism, hemoglobin subunit beta (p = 0.001) was significantly increased in AD compared to CN individuals. Multiple regression modeling adjusted for age, sex, APOE epsilon 4 genotype, and disease status in the AIBL cohort revealed lower levels of transferrin but higher levels of hemopexin associated with augmented brain amyloid deposition. Meanwhile, transferrin was positively associated with hippocampal volume and MMSE performance, and hemopexin was negatively associated with CDR scores. Partial correlation analysis revealed lack of significant associations between heme/iron proteins in the CN individuals progressing to cognitive impairment. Conclusions In conclusion, heme and iron dyshomeostasis appears to be a feature of AD. The causal relationship between heme/iron metabolism and AD warrants further investigation.