Optical spectroscopy to diagnose Alzheimer and Lewy body dementia

光谱诊断阿尔茨海默氏症和路易体痴呆症

• 批准号: 8958696
• 负责人: Eugene B. Hanlon
• 金额: --
• 依托单位: EDITH NOURSE ROGERS MEMORIAL VETERANS HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-10-01 至 2017-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8958696
• 关键词: Aging; Alzheimer' s Disease; Amyloid beta-Protein; Anatomy; Anxiety; Appearance; Autopsy; Biochemical; Biological Markers; Biopsy; Boston; Brain; Case Management; Cerebrospinal Fluid; Chronic Care; Classification; Clinical; Clinical Trials; Clinical assessments; Collection; Cost Savings; Dementia; Diagnosis; Diagnostic; Disease; Drug Targeting; Early Diagnosis; Enrollment; Family; Funding; Goals; Human; Image Analysis; Imaging Device; Incidence; Individual; Injury; Label; Lewy Bodies; Lewy Body Dementia; Life; Light; Link; Longitudinal Studies; Magnetic Resonance Imaging; Measurement; Medical Imaging; Mission; Monitor; Near-Infrared Spectroscopy; Neurofibrillary Tangles; Neurons; Optics; Pathology; Patient Care; Patients; Pharmaceutical Preparations; Phase; Pilot Projects; Plant Roots; Population; Positron-Emission Tomography; Prognostic Marker; Progress Reports; Recruitment Activity; Research; Risk; Spectrum Analysis; Spinal Puncture; Staging; Staining method; Stains; Subjects Selections; Symptoms; Technology; Therapeutic; Time; Tissues; Translating; Universities; Veterans; Work; age related; amyloid peptide; base; bench to bedside; brain tissue; chemical property; clinical care; cohort; cost effective; efficacy trial; in vivo; light scattering; mild cognitive impairment; nervous system disorder; neurodegenerative dementia; neuropathology; neuropsychological; next generation; optical spectra; outcome forecast; peptide A; point of care; pre-clinical; prevent; programs; protein aggregate; public health relevance; routine practice; screening; sound; tau Proteins; tool; treatment response

DESCRIPTION (provided by applicant): Progressive, irreversible, neuronal damage already has occurred by the time clinical symptoms of Alzheimer disease (AD) are documented. However, biochemical, histopathological and gross anatomic features of AD begin to appear during its insidious onset, preceding dementia by decades. Because of their value for diagnosis, screening, prognosis and as endpoints in clinical trials, enormous effort is being expended to define and detect early markers of AD, particularly utilizing established medical imaging approaches such as MRI and PET, and mildly invasive approaches such as lumbar puncture. However, a suitable tool for early diagnosis of MCI subjects who are likely convert to AD is non-invasive and can be routinely used at the point of care. Also, next generation drugs targeting the root causes of AD will need to identify and recruit subjects at very early stages of the disease, who otherwise will convert to advanced stage AD, because treatment, if successful, needs to start early, preferably in patients with mild cognitive impairment (MCI) due to AD or even asymptomatic subjects at the preclinical phase - again calling for practicable screening at the point of care. Currently, no clinically approved biomarker or imaging tool is available to identify such patients. The ability to identify MCI subjects who wil likely convert to AD and differentiate them from MCI non-converters will enable selection of the MCI converters as the most effective cohort for evaluating efficacy of trial therapeutics and will enable treatment, when available, at the earliest, most effective, stage of the disease. This proposal is to advance a relatively inexpensive, widely deployable and non-invasive approach for early detection at-point-of-care and progress monitoring of AD. Using technology developed under prior Merit funding, we show that near-infrared optical spectroscopy (NIR) can differentiate AD, MCI (mild cognitive impairment) and control patients. However, not all MCI patients convert to full blown AD. Near infrared light can propagate several centimeters through living tissue to reach the brain, completely non-invasively. Their inherent physical-chemical properties make plaques and tangles detectable optically, without stains or labels: they are dense protein aggregates, which scatter light characteristically. Thus, a direct connection between the observed NIR optical spectra and the known neuropathological features of disease is provided, in vivo. On the other hand, in the absence of biopsy and pathology, biological markers are the most direct diagnostic link to underlying disease. The concentration ratios of amyloid beta peptides to tau proteins in cerebrospinal fluid has emerged as the most clinically validated and quantified prognostic marker for AD to date. However, CSF collection is invasive and is not a routine practice for asymptomatic subjects. Herein we propose to demonstrate that NIR spectroscopy can provide a non- invasive, more readily accessible and equally accurate screen for incipient AD, while at the same time providing information complementary to MRI and PET.

描述（由申请人提供）： 在阿尔茨海默病（AD）的临床症状被记录时，已经发生了进行性的、不可逆的神经元损伤。然而，AD的生物化学、组织病理学和大体解剖学特征在其潜伏发作期间开始出现，在痴呆之前数十年。由于其在诊断、筛查、预后和临床试验终点方面的价值，人们正在花费巨大的努力来定义和检测AD的早期标志物，特别是利用已建立的医学成像方法（如MRI和PET）和轻度侵入性方法（如腰椎穿刺）。然而，用于可能转化为AD的MCI受试者的早期诊断的合适工具是非侵入性的，并且可以在护理点常规使用。此外，针对AD根本原因的下一代药物将需要识别和招募 处于疾病非常早期阶段的受试者，否则他们将转化为晚期AD，因为治疗如果成功，需要早期开始，最好是在患有AD所致轻度认知障碍（MCI）的患者中，甚至是在临床前阶段的无症状受试者中-再次要求在护理点进行切实可行的筛查。目前，没有临床批准的生物标志物 或者成像工具可用于识别这样的患者。鉴定可能转化为AD的MCI受试者并将其与MCI非转化者区分开的能力将使得能够选择MCI转化者作为用于评价试验治疗剂的功效的最有效群组，并且将使得能够在疾病的最早、最有效阶段进行治疗（当可用时）。 该提案旨在提出一种相对廉价、可广泛部署和非侵入性的方法，用于AD的早期检测和进展监测。使用在先前Merit资助下开发的技术，我们表明近红外光谱（NIR）可以区分AD，MCI（轻度认知障碍）和对照患者。然而，并非所有MCI患者都转化为完全AD。近红外光可以通过活体组织传播几厘米到达大脑，完全无创。它们固有的物理化学性质使得斑块和缠结可以在光学上检测到，而无需染色或标记：它们是致密的蛋白质聚集体，其特征性地散射光。因此，在体内提供了观察到的NIR光谱与疾病的已知神经病理学特征之间的直接联系。另一方面，在没有活检和病理学的情况下，生物标志物是与基础疾病最直接的诊断联系。脑脊液中淀粉样蛋白β肽与tau蛋白的浓度比已成为迄今为止最经临床验证和量化的AD预后标志物。然而，CSF采集是侵入性的，并且不是无症状受试者的常规做法。在此，我们提出证明NIR光谱可以为早期AD提供无创、更容易获得且同样准确的筛查，同时提供与MRI和PET互补的信息。