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: 9274906
• 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/9274906
• 关键词: Aging; Alzheimer disease detection; Alzheimer' s Disease; Amyloid beta-Protein; Anatomy; Anxiety; Appearance; Autopsy; Biochemical; Biological Markers; Biopsy; Boston; Brain; Case Management; Cerebrospinal Fluid; Characteristics; Chronic Care; Classification; Clinical; Clinical Trials; Clinical assessments; Collection; Cost Savings; Costs and Benefits; 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; Light; Link; Longitudinal Studies; Magnetic Resonance Imaging; Measurement; Medical Imaging; Mission; Monitor; Neurofibrillary Tangles; Neurons; Neuropsychology; 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; Staining method; Stains; Subjects Selections; Symptoms; Technology; Therapeutic Trials; Time; Tissues; Translating; Universities; Veterans; Work; age related; amyloid peptide; base; bench to bedside; brain tissue; chemical property; clinical Diagnosis; clinical care; cohort; cost effective; efficacy trial; imaging approach; in vivo; light scattering; mild cognitive impairment; mind control; nervous system disorder; neurodegenerative dementia; neuropathology; next generation; optical spectra; outcome forecast; 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)的临床症状被记录在案时，进行性的、不可逆转的神经元损伤已经发生。然而，阿尔茨海默病的生化、组织病理学和大体解剖特征开始出现在其隐匿的发病阶段，比痴呆早了几十年。由于它们在诊断、筛查、预后和临床试验中作为终点的价值，人们正在花费巨大的努力来定义和检测AD的早期标志物，特别是利用现有的医学成像方法，如MRI和PET，以及微创方法，如腰椎穿刺术。然而，对于可能转为AD的MCI受试者的早期诊断，一种合适的工具是非侵入性的，可以在护理时常规使用。此外，针对阿尔茨海默病根本原因的下一代药物将需要识别和招募 在疾病的非常早期阶段的受试者，他们将转变为晚期阿尔茨海默病患者，因为如果治疗成功，需要及早开始治疗，最好是在AD引起的轻度认知障碍(MCI)患者中，甚至在临床前阶段的无症状受试者中-再次呼吁在护理点进行可行的筛查。目前，还没有临床批准的生物标记物 或成像工具可用于识别此类患者。识别可能转变为AD的MCI受试者并将他们与MCI非转化者区分开来的能力，将使MCI转换者能够被选为评估试验疗法疗效的最有效的队列，并将能够在疾病的最早、最有效的阶段进行治疗。这项建议是为了推动一种相对便宜、可广泛部署和非侵入性的方法，用于在护理点进行早期检测和AD的进展监测。利用之前的Merit Funding开发的技术，我们证明了近红外光谱(NIR)可以区分AD、MCI(轻度认知障碍)和对照患者。然而，并不是所有的MCI患者都会转变为完全的AD。近红外线可以通过活组织传播几厘米到达大脑，完全是非侵入性的。它们固有的物理化学性质使斑块和缠结可以通过光学检测出来，没有污渍或标签：它们是致密的蛋白质聚集体，其特征是散射光线。因此，在活体中，观察到的近红外光谱与已知的疾病神经病理特征之间提供了直接的联系。另一方面，在没有活检和病理的情况下，生物标志物是对潜在疾病最直接的诊断联系。脑脊液中β淀粉样多肽与tau蛋白的浓度比已成为迄今为止临床验证和量化程度最高的AD预后指标。然而，脑脊液采集是侵入性的，并不是无症状受试者的常规做法。在这里，我们建议证明，近红外光谱可以为早期AD提供一种非侵入性的、更容易获得的、同样准确的筛查，同时提供补充MRI和PET的信息。

项目成果

Induced pluripotent stem cells (iPSCs) derived from frontotemporal dementia patient's peripheral blood mononuclear cells.

源自额颞叶痴呆患者外周血单核细胞的诱导多能干细胞（iPSC）。

• DOI: 10.1016/j.scr.2015.07.004
• 发表时间: 2015
• 期刊: Stem cell research
• 影响因子: 1.2
• 作者: Lee,Han-Kyu;Morin,Peter;Wells,John;Hanlon,EugeneB;Xia,Weiming
• 通讯作者: Xia,Weiming