Department of Ophthalmology, Boston Medical Center, Boston University School of Medicine, 85 E Concord St. #8813, Boston, MA, 02118, USA.
Department of Medicine (Biomedical Genetics Section), Boston University School of Medicine, Boston, MA, USA.
Alzheimers Res Ther. 2020 Sep 17;12(1):111. doi: 10.1186/s13195-020-00677-4.
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 Aβ (p = 7.7 × 10), Aβ (p = 2.8 × 10), and t-tau (p = 5.5 × 10), 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), IL-16 (p = 2.2 × 10), monocyte chemoattractant protein-1 (MCP1, p = 4.1 × 10), and vascular proteins such as vascular endothelial growth factor receptor-1 (VEGFR1, p = 2.9 × 10), Vegf-C (p = 8.6 × 10), vascular cell adhesion molecule-1 (VCAM-1, p = 5.0 × 10), Tie-2 (p = 6.3 × 10), and intracellular adhesion molecular-1 (ICAM-1, p = 1.6 × 10).
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.
神经丝轻链（NfL）是脑脊液和血液中神经退行性变的有前途的生物标志物。本研究调查了玻璃体液中 NfL 的存在及其与淀粉样β、tau、炎症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、全身疾病和眼部疾病的关系。
这是一项单站点、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（0.5-1.0ml），并抽取全血进行 APOE 基因分型。通过免疫测定定量测量玻璃体液中的 NfL、淀粉样β（Aβ）、总 Tau（t-Tau）、磷酸化 Tau（p-Tau181）、炎症细胞因子、趋化因子和血管蛋白。主要观察指标为检测玻璃体液中 NfL 水平及其与上述蛋白的相关性。线性回归用于在调整年龄、性别、教育水平和其他眼部疾病后，测试 NfL 与其他蛋白、APOE 基因型、MMSE 评分和眼部及全身疾病的相关性。
在所有 77 个玻璃体样本中均检测到 NfL。NfL 与眼部状况、APOE 基因型、MMSE 评分或全身疾病无相关性（p>0.05）。NfL 水平与玻璃体液中 Aβ（p=7.7×10）、Aβ（p=2.8×10）和 t-tau 的增加呈正相关，但与 p-tau181 无相关性（p=0.53）。NfL 还与炎症细胞因子如白细胞介素-15（IL-15，p=5.3×10）、白细胞介素-16（IL-16，p=2.2×10）、单核细胞趋化蛋白-1（MCP1，p=4.1×10）和血管蛋白如血管内皮生长因子受体-1（VEGFR1，p=2.9×10）、Vegf-C（p=8.6×10）、血管细胞黏附分子-1（VCAM-1，p=5.0×10）、Tie-2（p=6.3×10）和细胞间黏附分子-1（ICAM-1，p=1.6×10）有显著相关性。
NfL 可在眼部玻璃体液中检测到，并与玻璃体液中的淀粉样β、t-Tau 以及一些炎症和血管蛋白显著相关。此外，NfL 与患者的临床眼部状况无关。我们的研究结果为进一步研究 NfL 在眼液中的作用提供了基础，以了解其在眼部存在的潜在效用。
