Neurofilament light chain in the vitreous humor of the eye.
Neurofilament light chain in the vitreous humor of the eye.
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DOI：
10.1186/s13195-020-00677-4
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发表时间：
2020-09-17
期刊：
影响因子：
--
通讯作者：
Stein TD
中科院分区：
文献类型：
--
作者：
Subramanian ML;Vig V;Chung J;Fiorello MG;Xia W;Zetterberg H;Blennow K;Zetterberg M;Shareef F;Siegel NH;Ness S;Jun GR;Stein TD
神经丝轻链（NfL）是脑脊液和血液中神经退行性变的有希望的生物标志物。本研究调查了玻璃体液中NfL的存在及其与淀粉样蛋白β、tau、炎性细胞因子和血管蛋白、载脂蛋白E（APOE）基因型、简易精神状态检查（MMSE）评分、全身性疾病和眼科疾病的相关性。这是一项单中心、前瞻性、横断面队列研究。在玻璃体切除术期间抽吸未稀释的玻璃体液（0.5-1.0 mL），并抽取全血进行APOE基因分型。通过免疫测定法定量测量玻璃体中的NfL、淀粉样蛋白β（Aβ）、总Tau（t-Tau）、磷酸化Tau（p-Tau 181）、炎性细胞因子、趋化因子和血管蛋白。主要结果测量是玻璃体液中NfL水平的检测及其与上述蛋白质的相关性。在调整年龄、性别、教育水平和其他眼部疾病后，使用线性回归测试NfL与其他蛋白质、APOE基因型、MMSE评分以及眼科和全身疾病的关联。在所有77个玻璃体样品中检测到NfL。未发现NfL与眼科疾病、APOE基因型、MMSE评分或全身性疾病相关（p > 0.05）。NfL水平与Aβ40（p = 7.7 × 10−5）、Aβ42（p = 2.8 × 10−4）和t-tau（p = 5.5 × 10−7）玻璃体水平升高呈正相关，但与p-tau 181（p = 0.53）无关。NfL还与炎性细胞因子如白细胞介素-15有显著相关性（IL-15，p = 5.3 × 10−4），IL-16（p = 2.2 × 10−4），单核细胞趋化蛋白-1（MCP 1，p = 4.1 × 10−4）和血管蛋白，如血管内皮生长因子受体-1（VEGFR 1，p = 2.9 × 10−6）、Vegf-C（p = 8.6 × 10−6）、血管细胞粘附分子-1（VCAM-1，p = 5.0 × 10−4）、Tie-2（p = 6.3 × 10−4）和细胞内粘附分子-1（ICAM-1，p = 1.6 × 10−4）。NfL在眼睛的玻璃体液中是可检测的，并且与玻璃体中的淀粉样蛋白β、t-tau和选择的炎性和血管蛋白显著相关。此外，NfL与患者的临床眼部状况无关。我们的研究结果作为进一步研究眼内液中NfL的基础，以告知我们其在眼睛中存在的潜在效用。
Neurofilament light chain (NfL) is a promising biomarker of neurodegeneration in the cerebrospinal fluid and blood. This study investigated the presence of NfL in the vitreous humor and its associations with amyloid beta, tau, inflammatory cytokines and vascular proteins, apolipoprotein E (APOE) genotypes, Mini-Mental State Examination (MMSE) scores, systemic disease, and ophthalmic diseases. This is a single-site, prospective, cross-sectional cohort study. Undiluted vitreous fluid (0.5–1.0 mL) was aspirated during vitrectomy, and whole blood was drawn for APOE genotyping. NfL, amyloid beta (Aβ), total Tau (t-Tau), phosphorylated Tau (p-Tau181), inflammatory cytokines, chemokines, and vascular proteins in the vitreous were quantitatively measured by immunoassay. The main outcome measures were the detection of NfL levels in the vitreous humor and its associations with the aforementioned proteins. Linear regression was used to test the associations of NfL with other proteins, APOE genotypes, MMSE scores, and ophthalmic and systemic diseases after adjustment for age, sex, education level, and other eye diseases. NfL was detected in all 77 vitreous samples. NfL was not found to be associated with ophthalmic conditions, APOE genotypes, MMSE scores, or systemic disease (p > 0.05). NfL levels were positively associated with increased vitreous levels of Aβ40 (p = 7.7 × 10−5), Aβ42 (p = 2.8 × 10−4), and t-tau (p = 5.5 × 10−7), but not with p-tau181 (p = 0.53). NfL also had significant associations with inflammatory cytokines such as interleukin-15 (IL-15, p = 5.3 × 10−4), IL-16 (p = 2.2 × 10−4), monocyte chemoattractant protein-1 (MCP1, p = 4.1 × 10−4), and vascular proteins such as vascular endothelial growth factor receptor-1 (VEGFR1, p = 2.9 × 10−6), Vegf-C (p = 8.6 × 10−6), vascular cell adhesion molecule-1 (VCAM-1, p = 5.0 × 10−4), Tie-2 (p = 6.3 × 10−4), and intracellular adhesion molecular-1 (ICAM-1, p = 1.6 × 10−4). NfL is detectable in the vitreous humor of the eye and significantly associated with amyloid beta, t-tau, and select inflammatory and vascular proteins in the vitreous. Additionally, NfL was not associated with patients’ clinical eye condition. Our results serve as a foundation for further investigation of NfL in the ocular fluids to inform us about the potential utility of its presence in the eye.
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DOI：
10.1016/j.dadm.2017.10.005
发表时间：
2018
期刊：
Alzheimer's & dementia (Amsterdam, Netherlands)
影响因子：
--
作者：
den Haan J;Janssen SF;van de Kreeke JA;Scheltens P;Verbraak FD;Bouwman FH
通讯作者：
Bouwman FH
影响因子：
3.7
作者：
Cunha LP;Lopes LC;Costa-Cunha LV;Costa CF;Pires LA;Almeida AL;Monteiro ML
通讯作者：
Monteiro ML
影响因子：
7.3
作者：
Chen X;Hu Y;Cao Z;Liu Q;Cheng Y
通讯作者：
Cheng Y
影响因子：
3.4
作者：
Garcia-Martin, Elena;Bambo, Maria P.;Pablo, Luis E.
通讯作者：
Pablo, Luis E.
影响因子：
4
作者：
Gharbiya, Magda;Trebbastoni, Alessandro;De Lena, Carlo
通讯作者：
De Lena, Carlo