权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Iron as an Imaging Biomarker for Inflammation in AD

铁作为 AD 炎症的成像生物标志物

基本信息

批准号：
10538580
负责人：
MICHAEL M ZEINEH
金额：
$ 69.49万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-01-01 至 2024-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10538580
关键词：
Age Alzheimer&apos s Disease Alzheimer&apos s disease diagnosis Alzheimer&apos s disease pathology Alzheimer&apos s disease patient American Amyloid Amyloid beta-Protein Amyloid deposition Autopsy Biological Markers Brain Cells Clinical Complement Contralateral Coupling Data Dementia Deposition Development Disease Disease Outcome Early Diagnosis Eating Electron Microscopy Electrons Equilibrium Evaluation Fluorescence Free Radicals Frozen Sections Gender Globus Pallidus Goals Hippocampus Histologic Histology Human Image Immune Impairment Inflammation Iron Location Magnetic Resonance Imaging Magnetism Measurement Measures Memory Memory Loss Methods Microglia Microscopy Mission Myelin Nerve Degeneration Neurology Neuropsychology Non-Invasive Detection Participant Pathological Staging Pathology Patient Recruitments Patients Pattern Phase Positron-Emission Tomography Predisposition Process Proteins Protocols documentation Public Health Publishing Research Scanning Slide Spatial Distribution Specimen Spectrum Analysis Stains Surrogate Markers Symptoms Testing United States National Institutes of Health Visual Visualization X ray microscopy cognitive control effective therapy healthy aging histological stains imaging biomarker in vivo in vivo imaging inflammatory marker innovation insight materials science mild cognitive impairment multidisciplinary neuron loss neuropathology neurotoxicity novel novel strategies novel therapeutics outcome prediction oxidation spatial relationship tau Proteins tau aggregation ultra high resolution whole slide imaging

项目摘要

Alzheimer’s disease (AD) afflicts millions of Americans, but no effective treatments exist. Although abnormal proteins (amyloid and tau) accumulate and accompany neurodegeneration in AD, recent studies suggest that inflammation led by the brain’s immune cells (microglia) is an important factor. However, inflammation is challenging to measure in living patients. Iron is a key component of inflammation and may be toxic in AD. Because it can be measured by MRI, iron may be a practical surrogate measure for inflammation. Coupling MRI with pathology slides has shown that iron is present within microglia in AD, in particular in a part of the brain important for memory, the hippocampus. This project proposes that iron-containing microglia accumulate early in the disease process. The end result of this inflammation could be tau accumulation and neuronal death. If iron-containing microglia can be detected by MRI early in the disease process, before memory has become too impaired, this could revolutionize AD diagnosis and treatment. The project goals are as follows. (1) Determine whether the accumulation of iron-containing microglia is concomitant with widespread amyloid deposition and antecedent to tau propagation. This project will examine the post-mortem hippocampus of patients with and without AD pathology. By combining MRI with a careful examination of pathology slides, this project will prove that MRI is measuring iron-containing microglia across the stages of AD. We will also see how the iron, microglia, amyloid, and tau overlap with one another in human brain specimens. (2) Determine whether iron is higher in the hippocampus in AD compared to no AD using advanced microscopy. This project will employ X-ray microscopy and electron microscopy to measure exactly how much iron is in the hippocampus, and to define the precise location where it is increased in AD. (3) Determine whether iron-containing microglia are present along with amyloid and tau in living AD patients, present with along amyloid in patients with mild or no AD symptoms, and absent in patients with no amyloid. This proposal will recruit patients with AD, patients with mild cognitive impairment, and healthy control participants from Stanford’s Alzheimer’s Disease Research Center. We will balance for gender and age across groups, perform a full neuropsychological evaluation, and obtain APOE status. Participants will undergo three studies: a 7T GRE MRI, an amyloid PET-MR scan, and a tau PET-MR scan. This project will show how iron-containing microglia, amyloid, and tau overlap with one another in living humans. The contribution of this project will be to show that 7T GRE MR measures iron-containing microglia. This measurement can serve as an effective biomarker for inflammation in early AD. This project will enable many exciting opportunities to test new therapies before the onset of memory decline.

阿尔茨海默氏症(AD)困扰着数以百万计的美国人，但目前还没有有效的治疗方法。根据最近的研究，在AD中，异常蛋白质(淀粉样蛋白和Atau)可能会积聚，并可能伴随着神经退行性变。这表明，由大脑的小胶质细胞(小胶质细胞)引起的炎症是一个非常重要的危险因素。炎症性疾病是一种极具挑战性的方法，用来测量活体患者的血氧饱和度。铁质血是炎症性疾病的一个重要组成部分，而且可能也不是。在公元6月份，由于铁元素无法通过核磁共振进行测量，因此它可能不是治疗炎症的一种更实用的替代方法。将MRI检查与病理切片相结合表明，AD患者的小胶质细胞内也存在铁离子，尤其是其中的一部分。大脑中的一部分是记忆的重要组成部分，特别是海马体。这项研究项目提出了一种新的机制，即含有铁的小胶质细胞。在疾病发生的过程中积累早期的知识，但这种炎症的最终结果可能不是疾病的积累。神经元死亡。如果在疾病发生过程的早期，特别是在记忆之前，是否能通过核磁共振检查发现含铁的小胶质细胞。已经变得太弱了，但这项研究可能会给AD的诊断和治疗带来革命性的变化。该项目的目标如下：(1)确定含铁小胶质细胞的蓄积能力是否正常。伴随着广泛存在的淀粉样蛋白的沉积，以及影响tau基因繁殖的先天因素，这个新的项目将不会被研究。对60名患有AD和没有AD病理的患者的海马体进行了尸检。这是通过结合核磁共振检查和非常仔细的检查。通过对切片的病理检查，这个新的项目将证明我们的磁共振成像技术正在测量整个脑组织中含铁的小胶质细胞。我们还将看到人类体内的铁蛋白、小胶质细胞、淀粉样蛋白、蛋白质和酪蛋白是如何相互重叠的。脑组织标本。(2)将确定AD患者大脑海马区中的铁含量是否比未使用AD患者高。先进的电子显微镜。这个新的项目将使用X射线显微镜和电子显微镜来准确地测量。在海马体中有多少铁元素，以确定其确切的位置，以及在公元后增加的位置。在生活在AD患者中，是否存在含铁的小胶质细胞以及淀粉样蛋白和Ttau蛋白，以及它们是否存在。有轻度AD症状或无AD症状的患者有淀粉样蛋白，无淀粉样蛋白的患者有淀粉样蛋白缺失。但这项新的提案将有助于提高患者的生活质量。招募来自斯坦福大学的AD患者，有轻度认知功能障碍的患者，以及来自斯坦福大学的健康志愿者。阿尔茨海默氏症和疾病研究中心。我们将在不同群体中平衡性别差异和年龄差异，并全面发挥作用。神经心理学评估，并获得APOE状态。所有参与者将接受以下三项临床研究：7T、GRE和MRI。这个新的项目将展示含铁的小胶质细胞，也就是淀粉样蛋白。而在与人类生活的世界中，它们之间的关系相互重叠。这个项目的主要贡献率将不会被用来显示，7T和GRE先生的措施是含铁的小胶质细胞。在公元1世纪初，测量技术还可以作为一种有效的炎症性疾病的生物标志物。这项新的项目将使许多人能够。令人兴奋的是，在记忆力开始衰退之前，我们有机会测试各种新的治疗方法。

项目成果

期刊论文数量（14）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Hippocampal subfield imaging and fractional anisotropy show parallel changes in Alzheimer's disease tau progression using simultaneous tau-PET/MRI at 3T.

使用 3T 同步 tau-PET/MRI，海马亚场成像和分数各向异性显示阿尔茨海默病 tau 进展的平行变化。

DOI：
10.1002/dad2.12218
发表时间：
2021
期刊：
Alzheimer's & dementia (Amsterdam, Netherlands)
影响因子：
0
作者：
Carlson ML;Toueg TN;Khalighi MM;Castillo J;Shen B;Azevedo EC;DiGiacomo P;Mouchawar N;Chau G;Zaharchuk G;James ML;Mormino EC;Zeineh MM
通讯作者：
Zeineh MM

Correlative Microscopy to Localize and Characterize Iron Deposition in Alzheimer's Disease.

DOI：
10.3233/adr-200234
发表时间：
2020-12-21
期刊：
Journal of Alzheimer's disease reports
影响因子：
0
作者：
Madsen SJ;DiGiacomo PS;Zeng Y;Goubran M;Chen Y;Rutt BK;Born D;Vogel H;Sinclair R;Zeineh MM
通讯作者：
Zeineh MM

Comparison of diffusion MRI and CLARITY fiber orientation estimates in both gray and white matter regions of human and primate brain.

DOI：
10.1016/j.neuroimage.2020.117692
发表时间：
2021-03
期刊：
NeuroImage
影响因子：
5.7
作者：
Leuze C;Goubran M;Barakovic M;Aswendt M;Tian Q;Hsueh B;Crow A;Weber EMM;Steinberg GK;Zeineh M;Plowey ED;Daducci A;Innocenti G;Thiran JP;Deisseroth K;McNab JA
通讯作者：
McNab JA

Investigating Simultaneity for Deep Learning-Enhanced Actual Ultra-Low-Dose Amyloid PET/MR Imaging.

研究深度学习增强的实际超低剂量淀粉样蛋白 PET/MR 成像的同时性。

DOI：
10.3174/ajnr.a7410
发表时间：
2022
期刊：
AJNR. American journal of neuroradiology
影响因子：
0
作者：
Chen,KT;Adeyeri,O;Toueg,TN;Zeineh,M;Mormino,E;Khalighi,M;Zaharchuk,G
通讯作者：
Zaharchuk,G

Iron and Alzheimer's Disease: From Pathology to Imaging.

DOI：
10.3389/fnhum.2022.838692
发表时间：
2022
期刊：
FRONTIERS IN HUMAN NEUROSCIENCE
影响因子：
2.9
作者：
Tran, Dean;DiGiacomo, Phillip;Born, Donald E.;Georgiadis, Marios;Zeineh, Michael
通讯作者：
Zeineh, Michael