用于阿尔茨海默病筛查和诊断的泪液生物标志物（TearAD 研究）：一项观察性纵向多中心研究的设计和原理。
Tear biomarkers for Alzheimer's disease screening and diagnosis (the TearAD study): design and rationale of an observational longitudinal multicenter study.
机构信息
School of Mental Health and Neuroscience (MHeNs), University Eye Clinic Maastricht, Maastricht University, Maastricht, The Netherlands.
Department of Psychiatry and Neuropsychology, Alzheimer Center Limburg, School of Mental Health and Neuroscience (MHeNs), Maastricht University, Maastricht, The Netherlands.
出版信息
BMC Neurol. 2023 Aug 5;23(1):293. doi: 10.1186/s12883-023-03335-y.
BACKGROUND
Alzheimer's disease (AD) is the most common cause of dementia, and due to increasing life expectancy the number of patients is expected to grow. The diagnosis of AD involves the use of biomarkers determined by an amyloid PET scan or cerebrospinal fluid analyses that are either invasive or expensive, and not available in each hospital, thus limiting their usage as a front-line screener. The TearAD study aims to use tear fluid as a potential source for AD biomarkers. In previous reports, we demonstrated that AD biomarkers amyloid-beta and tau, are measurable in tear fluid and are associated with disease severity and neurodegeration. This study aims to validate previous results in a larger cohort and evaluate the diagnostic accuracy of tear biomarkers to discriminate between individuals with and without neurodegeneration as determined by hippocampal atrophy.
METHODS
The TearAD study is an observational longitudinal multi-center study that will enroll 50 cognitively healthy controls, 50 patients with subjective cognitive decline, 50 patients with mild cognitive impairment and 50 patients with AD dementia from the memory clinic. Participants will be examined at baseline, after one year, and after two years follow-up. Study assessments include neuropsychological tests and ophthalmic examination. All participants will receive a MRI scan, and a subset of the study population will undergo cerebral spinal fluid collection and an amyloid PET scan. Tear fluid will be collected with Schirmer strips and levels of Aβ38, Aβ40, Aβ42, t-tau and p-tau in tear fluid will be determined using multiplex immunoassays. Blood samples will be collected from all participants. Images of the retina will be obtained with a standard, hyperspectral and ultra-wide field fundus camera. Additionally, macular pigment optical density will be measured with the macular pigment reflectometer, and cross-sectional images of the retina will be obtained through optical coherence tomography imaging.
DISCUSSION
The TearAD study will provide insight into the potential diagnostic use of tear biomarkers as a minimally invasive and low cost tool for the screening and diagnosis of AD.
TRIAL REGISTRATION
Retrospectively registered at clinicaltrials.gov (NCT05655793).
背景
阿尔茨海默病（AD）是痴呆症最常见的病因，由于预期寿命的延长，患者人数预计将会增加。AD 的诊断涉及使用通过淀粉样 PET 扫描或脑脊液分析确定的生物标志物，这些生物标志物具有侵入性或昂贵，并且并非每个医院都有，因此限制了它们作为一线筛查工具的使用。TearAD 研究旨在使用泪液作为 AD 生物标志物的潜在来源。在之前的报告中，我们证明了 AD 生物标志物淀粉样蛋白-β和 tau 可以在泪液中测量，并且与疾病严重程度和神经退行性变相关。本研究旨在更大的队列中验证先前的结果，并评估泪液生物标志物的诊断准确性，以区分有和无海马萎缩所致神经退行性变的个体。
方法
TearAD 研究是一项观察性纵向多中心研究，将从记忆诊所招募 50 名认知健康对照者、50 名有主观认知下降者、50 名有轻度认知障碍者和 50 名有 AD 痴呆者。参与者将在基线、一年后和两年随访时进行检查。研究评估包括神经心理学测试和眼科检查。所有参与者将接受 MRI 扫描，部分研究人群将接受脑脊液采集和淀粉样蛋白 PET 扫描。泪液将使用 Schirmer 条采集，泪液中的 Aβ38、Aβ40、Aβ42、t-tau 和 p-tau 水平将使用多重免疫分析确定。所有参与者都将采集血样。将使用标准、高光谱和超广角眼底相机获取视网膜图像。此外，将使用黄斑色素反射计测量黄斑色素光密度，并通过光学相干断层扫描成像获取视网膜的横截面图像。
讨论
TearAD 研究将提供有关泪液生物标志物作为 AD 筛查和诊断的微创、低成本工具的潜在诊断用途的见解。
试验注册
在 clinicaltrials.gov 上进行了回顾性注册（NCT05655793）。
Zotero 插件