The Contribution of Age-Related Taupahtoies to Alzheimer's Disease-Supplement

与年龄相关的 Taupahtoies 对阿尔茨海默病补充剂的贡献

基本信息

批准号：
10652169
负责人：
John Fonda Crary
金额：
$ 41.25万
依托单位：
BOSTON UNIVERSITY MEDICAL CAMPUS
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-30 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10652169
关键词：
Affect Aggressive behavior Aging Agitation Alzheimer disease prevention Alzheimer&apos s Disease Amygdaloid structure Anxiety Argyrophilic Grain Disease Blood Vessels Boston Brain Brain Diseases Brain region Clinic Clinical Cognition Cognitive Data Data Set Databases Dementia Deposition Detection Diagnosis Diagnostic Diagnostic Errors Digital Libraries Discrimination Disease Elderly Episodic memory Frequencies Goals Health Hippocampus (Brain)Impaired cognition Individual Inflammatory Investigation Knowledge Lead Lewy Body Disease Memory Disorders Mental Depression Mission Molecular Nerve Degeneration Neurodegenerative Disorders Pathologic Pathology Patients Pattern Personal Satisfaction Phenotype Prefrontal Cortex Protocols documentation Public Health Reproducibility Research Research Personnel Sampling Severities Sleep disturbances Slide Standardization Subgroup Tauopathies Therapeutic Tissues Universities age related aged base chronic traumatic encephalopathy clinical diagnosis comorbidity demented diagnostic strategy diagnostic tool diagnostic value end of life frontal lobe improved inflammatory marker insight mild cognitive impairment neuroinflammation neuropathology neuropsychiatric symptom neuropsychiatry novel novel diagnostics protein TDP-43 tau Proteins tau mutation therapeutically effective

项目摘要

Establishing an accurate neuropathological diagnosis is a critical function of Alzheimer’s Disease Research Center (ADRC) Neuropathology Cores and is a prerequisite for all tissue-based research. Chronic traumatic encephalopathy (CTE), primary age-related tauopathy (PART), argyrophilic grain disease (AGD) and aging- related tau astrogliopathy (ARTAG) are all age-related tauopathies, yet each has distinctive patterns of abnormal tau deposition. Criteria to diagnose CTE, PART, AGD and ARTAG have been recently proposed, yet no modules exist to capture these disorders in the National Alzheimer’s Disease Coordinating Center (NACC) database. Without rigorous, reproducible protocols for the diagnosis of age-related tauopathies, disease-specific contributors to late life cognitive decline might be overlooked, confused, and obscured. Twenty-nine Alzheimer Disease Research Centers across the U.S. contribute neuropathological data to the National Alzheimer's Coordinating Center - Neuropathology Data Set (NACC-NDS), making the NACC-NDS one of the largest publicly accessible neuropathological datasets on AD and related disorders in the world. In this proposal we will draw on the neuropathological expertise of Dr. Ann McKee, Dr. Dennis Dickson, and Dr. John Crary, who have pioneered investigations of CTE, AGD and PART. We will use 152 cases of AD and age-related tauopathies from the Boston University, Mayo Clinic Jacksonville, and Mount Sinai ADCs to identiify novel tau and inflammatory markers to detect and distinguish the disorders. We will also establish the frequency of CTE, PART, AGD and ARTAG among 600 cognitively normal, mild cognitively impaired and demented subjects in the NACC-NDS with NACC-Uniform Data Set (UDS) diagnosis and determine the contribution of these disorders to clinical diagnosis and cognitive and neuropsychiatric profile. We will apply knowledge gained from this project to develop CTE, PART, AGD and ARTAG assessment modules and provisional criteria to neuropathologically differentiate the age-related tauopathies for general use. This proposal will answer a critically unmet need in the study of neurodegeneration. Specifically, it will identify novel tau and neuroinflammatory markers in CTE, PART, AGD and ARTAG to aid in their detection and discrimination. This project will also determine the frequency of these age-related tauopathies among memory disorder clinic patients and determine whether these disorders contribute to the clinical profile. In addition, this project will develop a digital library of immunostained slides from 600 NACC cases (200 normal cognition, 200 MCI, 200 dementia) with UDS phenotyping that will be available to other ADRC and NACC investigators. This research has the potential to transform the way we conceptualize MCI and dementia, and ultimately, develop more effective therapeutic strategies, by developing harmonized criteria for the diagnosis of distinct disorders that contribute to the clinical diagnosis, cognitive and neuropsychiatric profile, and neuropathological phenotype of memory disorders patients.

建立准确的神经病理学诊断是阿尔茨海默病研究的关键功能中心（ADRC）神经病理学核心，是所有基于组织的慢性创伤研究的先决条件。脑病 (CTE)、原发性年龄相关 tau 蛋白病 (PART)、嗜银颗粒病 (AGD) 和衰老相关 tau 星形胶质细胞病 (ARTAG) 都是与年龄相关的 tau 蛋白病，但每种都有独特的异常模式最近提出了诊断 CTE、PART、AGD 和 ARTAG 的标准，但还没有模块。国家阿尔茨海默病协调中心 (NACC) 数据库中存在这些疾病。如果没有严格的、可重复的方案来诊断与年龄相关的 tau蛋白病，疾病特异性导致晚年认知能力下降的因素可能会被忽视、混淆和掩盖。二十九阿尔茨海默病。美国各地的疾病研究中心向国家阿尔茨海默病研究中心提供神经病理学数据协调中心 - 神经病理学数据集 (NACC-NDS)，使 NACC-NDS 成为最大的公开数据集之一在本提案中，我们将利用世界上可访问的 AD 和相关疾病的神经病理学数据集。 Ann McKee 博士、Dennis Dickson 博士和 John Crary 博士的神经病理学专业知识，他们是我们将使用 152 例 AD 和年龄相关的 tau蛋白病病例进行 CTE、AGD 和 PART 的研究。波士顿大学、梅奥诊所杰克逊维尔和西奈山 ADC 鉴定新型 tau 蛋白和炎症我们还将确定 CTE、PART、AGD 和疾病的频率。 ARTAG 在 NACC-NDS 中的 600 名认知正常、轻度认知障碍和痴呆受试者中进行 NACC-统一数据集（UDS）诊断并确定这些疾病对临床诊断的贡献我们将应用从该项目中获得的知识来开发 CTE， PART、AGD 和 ARTAG 评估模块和临时标准，用于从神经病理学角度区分该提案将解决与年龄相关的 tau蛋白病研究中严重未满足的需求。具体来说，它将识别 CTE、PART、AGD 中的新型 tau 蛋白和神经炎症标记物。和 ARTAG 来帮助检测和区分，该项目还将确定这些的频率。记忆障碍诊所患者中与年龄相关的tau蛋白病，并确定这些疾病是否此外，该项目将开发一个免疫染色载玻片数字库 600 例 NACC 病例（200 例正常认知，200 例 MCI，200 例痴呆）具有 UDS 表型分析，可用于其他 ADRC 和 NACC 研究人员这项研究有可能改变我们的概念化方式。 MCI 和痴呆症，并最终通过制定协调一致的方法来制定更有效的治疗策略有助于临床诊断的不同疾病的诊断标准，以及记忆障碍患者的神经精神特征和神经病理表型。