Eye to Brain: Eye Biomarkers and Cognition

眼对脑：眼睛生物标志物和认知

• 批准号: 9910353
• 负责人: Manju Subramanian
• 金额: $ 17.35万
• 依托单位: BOSTON MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-15 至 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9910353
• 关键词: Academic Medical Centers; Alzheimer disease detection; Alzheimer' s Disease; Alzheimer' s disease diagnosis; Amyloid beta-42; Amyloid beta-Protein; Animals; Aqueous Humor; Autopsy; Biological Markers; Boston; Brain; Cerebrospinal Fluid; Clinical; Cognition; Cognitive; Data; Detection; Diagnosis; Diagnostic; Diagnostic tests; Disease; Early Diagnosis; Enrollment; Enzyme-Linked Immunosorbent Assay; Eye; Eye diseases; Ganglion Cell Layer; Goals; Human; Image; Knowledge; Liquid substance; Nerve Degeneration; Nerve Fibers; Neurologic Signs; Ophthalmology; Optic Nerve; Optical Coherence Tomography; Outpatients; Patients; Peptides; Pilot Projects; Play; Predictive Value; Procedures; Proteins; Research; Retina; Role; Sampling; Testing; Therapeutic; Thick; Vitreous humor; aqueous; base; brain tissue; cognitive function; cognitive testing; cohort; digital; mental state; nervous system disorder; neuropathology; novel; ocular imaging; optical imaging; prognostic value; protein biomarkers; retinal imaging; tau Proteins; tool

PROJECT SUMMARY The goal of our research is to identify ocular biomarkers that have diagnostic and potentially prognostic utility in Alzheimer's Disease (AD), and establish a relationship to cognition. We seek to determine this relationship in an already established cohort of patients (the Vitreous Biomarkers Study, or VBS) with eye disease where protein biomarkers have been identified in the vitreous humor of the eye and found to be correlated to cognitive function scores on mini-mental status examination (MMSE). There is a need for sensitive and specific diagnostic tests that can detect AD in the early stages. We hypothesize that ocular levels of Aβ and Tau in the aqueous humor of the eye as well as retinal biomarkers of neurodegeneration imaged by Optical Coherence Tomography (OCT), combined with cognitive assessments, may offer a predictive value for detection of early AD. In the VBS, we found that levels of beta amyloid (Aβ40, Aβ42), and total Tau (tTau) in the vitreous humor are correlated with cognitive function scores obtained by mini-mental status examination (MMSE). Drawing from the same patient cohort, we seek to establish the presence of the same proteins in the aqueous humor of the eye (which is more clinically accessible than the vitreous humor), obtain OCT images to look for retinal biomarkers, and repeat MMSE testing to look longitudinally at cognition, and correlate all eye biomarkers with cognition. Additionally, we seek to validate the protein levels in the aqueous and vitreous humor of eyes from postmortem subjects. If a relationship of protein and retinal biomarkers to cognition can be shown, our knowledge of the eye's role in AD will be increased substantially and it will establish the eye as potentially playing a central role in how we diagnose AD.

项目概要 我们研究的目标是确定具有诊断和潜在预后用途的眼部生物标志物 阿尔茨海默病（AD），并与认知建立关系。我们试图确定这种关系 已经建立的患有眼病的患者队列（玻璃体生物标志物研究，或 VBS），其中 已在眼睛玻璃体液中鉴定出蛋白质生物标志物，并发现其与认知能力相关 简易精神状态检查（MMSE）的功能评分。需要敏感且具体的 可以在早期阶段检测 AD 的诊断测试。我们假设 Aβ 和 Tau 的眼部水平 通过光学成像的眼房水以及神经退行性变的视网膜生物标志物 相干断层扫描 (OCT) 与认知评估相结合，可以提供预测价值 早期 AD 的检测。在 VBS 中，我们发现 β 淀粉样蛋白（Aβ40、Aβ42）和总 Tau（tTau）的水平 玻璃体液与简易精神状态检查获得的认知功能评分相关 （MMSE）。我们从同一患者队列中提取数据，试图确定相同蛋白质的存在 眼房水（临床上比玻璃体液更容易接近），获取 OCT 图像以 寻找视网膜生物标志物，并重复 MMSE 测试以纵向观察认知，并将所有眼睛关联起来 具有认知能力的生物标志物。此外，我们试图验证房水和玻璃体中的蛋白质水平 死后受试者眼睛里的幽默。如果蛋白质和视网膜生物标志物与认知的关系可以 表明，我们对眼睛在 AD 中的作用的认识将大大增加，并将使眼睛成为 可能在我们如何诊断 AD 方面发挥核心作用。

项目成果

Protein and Imaging Biomarkers in the Eye for Early Detection of Alzheimer's Disease.

• DOI: 10.3233/adr-210283
• 发表时间: 2021-05-03
• 期刊: Journal of Alzheimer's disease reports
• 作者: Fereshetian S;Agranat JS;Siegel N;Ness S;Stein TD;Subramanian ML
• 通讯作者: Subramanian ML

Upregulation of Neuroinflammatory Protein Biomarkers in Acute Rhegmatogenous Retinal Detachments.

• DOI: 10.3390/life13010118
• 发表时间: 2022-12-31
• 期刊: LIFE-BASEL
• 影响因子: 3.2
• 作者: Prasad, Minali;Xu, Jia;Agranat, Joshua S.;Xia, Weiming;Daley, Sarah;Ness, Steven;Chen, Xuejing;Siegel, Nicole H.;Stein, Thor D.;Chung, Jaeyoon;Subramanian, Manju L.
• 通讯作者: Subramanian, Manju L.

Neurofilament light chain in the vitreous humor of the eye.

• DOI: 10.1186/s13195-020-00677-4
• 发表时间: 2020-09-17
• 期刊: Alzheimer's research & therapy
• 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
• 通讯作者: Stein TD

Cytokine Levels in Human Vitreous in Proliferative Diabetic Retinopathy.

• DOI: 10.3390/cells10051069
• 发表时间: 2021-04-30
• 期刊: Cells
• 影响因子: 6
• 作者: Loporchio DF;Tam EK;Cho J;Chung J;Jun GR;Xia W;Fiorello MG;Siegel NH;Ness S;Stein TD;Subramanian ML
• 通讯作者: Subramanian ML