Sternberg Zohara, Podolsky Rebecca, Nir Adam, Yu Jihnhee, Nir Raphael, Halvorsen Stanley W, Quinn Joseph F, Kaye Jeffrey, Kolb Channa
Department of Neurology, Stroke Center, Buffalo Medical Center, Buffalo, NY, USA.
Department of Neurology, Stroke Center, Buffalo Medical Center, Buffalo, NY, USA.
J Clin Neurosci. 2022 Jun;100:169-174. doi: 10.1016/j.jocn.2022.04.028. Epub 2022 Apr 26.
BACKGROUND/AIMS: There is a close link between iron and polyamine biosynthesis and metabolism. In a recent study, we reported alterations in the serum levels of hepcidin and other iron-related proteins in Alzheimer's disease (AD) patients (Sternberg et al., 2017). Based on these findings, this pilot study compared serum levels of one of the polyamines, Spermidine, between AD, mild cognitive impairment (MCI), and control subjects, correlating the levels with the existing clinical and neuroimaging data.
This cross-sectional study measured Spermidine levels in frozen serum samples of 43 AD patients, 12 MCI patients, and 21 age-matched controls, provided by the Oregon Alzheimer's Disease Center Bio-repository, using enzyme-linked immunosorbent assay.
MCI patients showed significantly higher mean Spermidine serum levels compared to controls (P = 0.01), with a non-significant trend for higher Spermidine serum levels in pure AD (P = 0.08) participants compared to controls. Spermidine serum levels correlated with the values of cognitive assessment tests including MMSE (r = -0.705, P = 0.003), CDR (r = 0.751, P = 0.002), and CDR-SOB (r = 0.704, P = 0.007), in "pure" AD subgroup, suggesting that higher Spermidine serum levels in MCI can be a potential biomarker of conversion to dementia in subjects with AD underlying pathology. Furthermore, Spermidine serum levels correlated with serum levels of the chief iron regulatory protein, hepcidin in AD participants with a more advanced disease stage, indicated by MMSE (strata of 8-19, P = 0.02), and CDR-SOB (strata of 6-12, P = 0.03).
Studies with larger cohort are warranted for defining the role of Spermidine in AD pathophysiology, and the utility of polyamines as biomarkers of progression of MCI to AD.
背景/目的：铁与多胺的生物合成及代谢之间存在紧密联系。在最近一项研究中，我们报道了阿尔茨海默病（AD）患者血清中铁调素及其他铁相关蛋白水平的变化（斯特恩伯格等人，2017年）。基于这些发现，本初步研究比较了AD患者、轻度认知障碍（MCI）患者及对照受试者中多胺之一——亚精胺的血清水平，并将这些水平与现有的临床和神经影像学数据相关联。
这项横断面研究使用酶联免疫吸附测定法，检测了俄勒冈州阿尔茨海默病中心生物样本库提供的43例AD患者、12例MCI患者及21例年龄匹配对照者的冷冻血清样本中亚精胺水平。
与对照组相比，MCI患者的亚精胺血清平均水平显著更高（P = 0.01），与对照组相比，单纯AD患者（P = 0.08）的亚精胺血清水平有升高趋势，但无统计学意义。在“单纯”AD亚组中，亚精胺血清水平与包括简易精神状态检查表（MMSE，r = -0.705，P = 0.003）、临床痴呆评定量表（CDR，r = 0.751，P = 0.002）及CDR-总衰退量表（CDR-SOB，r = 0.704，P = 0.007）在内的认知评估测试值相关，这表明MCI中亚精胺血清水平升高可能是具有AD潜在病理的受试者向痴呆转化的潜在生物标志物。此外，在疾病阶段更严重的AD参与者中，亚精胺血清水平与主要铁调节蛋白——铁调素的血清水平相关，这由MMSE（8 - 19分层，P = 0.02）及CDR-SOB（6 - 12分层，P = 0.03）表明。
需要开展更大样本队列研究来确定亚精胺在AD病理生理学中的作用，以及多胺作为MCI进展为AD的生物标志物的效用。
