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）： 当阿尔茨海默病 (AD) 的临床症状被记录下来时，进行性、不可逆的神经元损伤已经发生。然而，AD 的生化、组织病理学和大体解剖学特征在其隐匿发作期间开始显现，比痴呆早了数十年。由于它们对于诊断、筛查、预后以及作为临床试验终点的价值，人们正在付出巨大的努力来定义和检测 AD 的早期标志物，特别是利用现有的医学成像方法（如 MRI 和 PET）以及轻度侵入性方法（如腰椎穿刺）。然而，对于可能转化为 AD 的 MCI 受试者来说，有一种合适的早期诊断工具是非侵入性的，并且可以在护理时常规使用。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，否则他们将转变为晚期 AD，因为治疗如果成功，需要尽早开始，最好是 AD 引起的轻度认知障碍 (MCI) 患者，甚至是临床前阶段的无症状受试者 - 再次呼吁在护理点进行切实可行的筛查。目前尚无临床批准的生物标志物 或成像工具可用于识别此类患者。识别可能转化为 AD 的 MCI 受试者并将其与 MCI 未转化者区分开来的能力，将能够选择 MCI 转化者作为评估试验治疗效果的最有效队列，并在可用时在疾病的最早、最有效的阶段实现治疗。 该提案旨在推进一种相对便宜、可广泛部署和非侵入性的方法，用于 AD 的早期护理点检测和进展监测。使用先前 Merit 资助下开发的技术，我们证明近红外光谱 (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 患者都会转变为完全的 AD。近红外光可以通过活组织传播几厘米到达大脑，完全无创。它们固有的物理化学特性使得斑块和缠结可以光学检测，无需染色或标签：它们是致密的蛋白质聚集体，具有特征性的散射光。因此，在体内提供了观察到的近红外光谱与已知的疾病神经病理学特征之间的直接联系。另一方面，在缺乏活检和病理学的情况下，生物标志物是与潜在疾病最直接的诊断联系。脑脊液中β淀粉样蛋白肽与tau蛋白的浓度比已成为迄今为止临床上最有效和量化的AD预后标志物。然而，脑脊液采集是侵入性的，对于无症状受试者来说并不是常规做法。在此，我们建议证明近红外光谱可以为早期 AD 提供非侵入性、更容易访问且同样准确的筛查，同时提供与 MRI 和 PET 互补的信息。