Immunomodulatory sphingosine-1-phosphates as plasma biomarkers of Alzheimer's disease and vascular cognitive impairment.
Immunomodulatory sphingosine-1-phosphates as plasma biomarkers of Alzheimer's disease and vascular cognitive impairment.
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免疫调节鞘氨醇-1-磷酸作为阿尔茨海默病和血管性认知障碍的血浆生物标志物
DOI：
10.1186/s13195-020-00694-3
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发表时间：
2020-09-30
期刊：
影响因子：
--
通讯作者：
Lai MKP
中科院分区：
文献类型：
--
作者：
Chua XY;Chai YL;Chew WS;Chong JR;Ang HL;Xiang P;Camara K;Howell AR;Torta F;Wenk MR;Hilal S;Venketasubramanian N;Chen CP;Herr DR;Lai MKP
人们一直在致力于发现阿尔茨海默病 (AD)、血管性痴呆 (VaD) 和血管性认知障碍 (VCI) 范围内相关脑血管疾病 (CEVD) 相关疾病的新型血液诊断和预后生物标志物。 1-磷酸鞘氨醇 (S1P) 是信号脂质，作用于同源 G 蛋白偶联受体的 S1PR 家族，并已被证明可以调节神经炎症，这一过程已知与神经退行性疾病和脑血管疾病有关。然而，外周S1P在AD和VCI中的状态目前尚不清楚。我们从正在进行的纵向队列研究中招募的认知正常的个体中获取了基线血液（N = 80）；认知障碍，无痴呆（N = 160）； AD (N = 113);或 VaD (N = 31)，以及脑血管疾病的神经影像评估。对血浆样本进行处理以测量主要 S1P 种类：d16:1、d17:1、d18:0 和 d18:1，以及促炎细胞因子白细胞介素 (IL)-6、IL-8 和肿瘤坏死因子 (TNF)。此外，还在星形细胞瘤细胞系和啮齿动物原代星形胶质细胞中研究了 S1P 对细胞因子表达的体外影响。在测量的 S1P 种类中，VaD 患者血浆中只有 d16:1 S1P 显着降低，而 AD 患者血浆中则没有显着降低，而所有认知亚组（CIND、AD 和 VaD）中 d18:1 与 d16:1 的比率均增加。此外，d18:1 至 d16:1 比率与 IL-6、IL-8 和 TNF 水平相关。在原代星形胶质细胞和星形胶质细胞系中，用 d16:1 或 d18:1 S1P 处理会导致促炎细胞因子 mRNA 转录物上调，其中 d18:1 的效果比 d16:1 更强。有趣的是，联合治疗测定表明，添加 d16:1 降低了 d18:1 介导的基因表达程度，表明 d16:1 可能具有“微调”d18:1 的促炎作用。综上所述，我们的数据表明，血浆 d16:1 S1P 可用作 VCI 的诊断标志物，而 d18:1 与 d16:1 S1P 比率是 S1P 介导的免疫调节失调的指标，导致慢性炎症相关的神经变性和脑血管损伤。
There has been ongoing research impetus to uncover novel blood-based diagnostic and prognostic biomarkers for Alzheimer’s disease (AD), vascular dementia (VaD), and related cerebrovascular disease (CEVD)-associated conditions within the spectrum of vascular cognitive impairment (VCI). Sphingosine-1-phosphates (S1Ps) are signaling lipids which act on the S1PR family of cognate G-protein-coupled receptors and have been shown to modulate neuroinflammation, a process known to be involved in both neurodegenerative and cerebrovascular diseases. However, the status of peripheral S1P in AD and VCI is at present unclear. We obtained baseline bloods from individuals recruited into an ongoing longitudinal cohort study who had normal cognition (N = 80); cognitive impairment, no dementia (N = 160); AD (N = 113); or VaD (N = 31), along with neuroimaging assessments of cerebrovascular diseases. Plasma samples were processed for the measurements of major S1P species: d16:1, d17:1, d18:0, and d18:1, along with pro-inflammatory cytokines interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF). Furthermore, in vitro effects of S1Ps on cytokine expression were also studied in an astrocytoma cell line and in rodent primary astrocytes. Of the S1Ps species measured, only d16:1 S1P was significantly reduced in the plasma of VaD, but not AD, patients, while the d18:1 to d16:1 ratios were increased in all cognitive subgroups (CIND, AD, and VaD). Furthermore, d18:1 to d16:1 ratios correlated with levels of IL-6, IL-8, and TNF. In both primary astrocytes and an astroglial cell line, treatment with d16:1 or d18:1 S1P resulted in the upregulation of mRNA transcripts of pro-inflammatory cytokines, with d18:1 showing a stronger effect than d16:1. Interestingly, co-treatment assays showed that the addition of d16:1 reduced the extent of d18:1-mediated gene expression, indicating that d16:1 may function to “fine-tune” the pro-inflammatory effects of d18:1. Taken together, our data suggest that plasma d16:1 S1P may be useful as a diagnostic marker for VCI, while the d18:1 to d16:1 S1P ratio is an index of dysregulated S1P-mediated immunomodulation leading to chronic inflammation-associated neurodegeneration and cerebrovascular damage.
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影响因子：
7.3
作者：
Galvani S;Sanson M;Blaho VA;Swendeman SL;Obinata H;Conger H;Dahlbäck B;Kono M;Proia RL;Smith JD;Hla T
通讯作者：
Hla T
影响因子：
1.6
作者：
Chai YL;Hilal S;Chong JPC;Ng YX;Liew OW;Xu X;Ikram MK;Venketasubramanian N;Richards AM;Lai MKP;Chen CP
通讯作者：
Chen CP
1-磷酸盐的出口和功能。
DOI：
10.1016/j.bbalip.2009.02.011
发表时间：
2009-07
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Kim RH;Takabe K;Milstien S;Spiegel S
通讯作者：
Spiegel S
影响因子：
3.4
作者：
Azizkhanian, Ida;Sheth, Sunil A.;Hinman, Jason D.
通讯作者：
Hinman, Jason D.
影响因子：
3.7
作者：
Godfrey, Jessica;Jeanguenin, Lisa;Brasser, Susan M.
通讯作者：
Brasser, Susan M.