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氏病研究的关键功能中心（ADRC）神经病理学核心，是所有基于组织研究的先决条件。慢性创伤脑病（CTE），初级与年龄相关的双胞胎病（部分），杂粒谷物疾病（AGD）和衰老相关的tau星形胶质病（ARTAG）都是与年龄相关的tauopathies，但每种都有独特的异常模式 tau沉积。最近提出了诊断CTE，部分，AGD和ARTAG的标准，但没有模块存在于国家阿尔茨海默氏病协调中心（NACC）数据库中捕获这些疾病。没有严格的可再现方案，用于诊断与年龄相关的tauopathies，疾病特异性促使后期认知能力下降的贡献者可能会被忽视，困惑和掩盖。二十九个阿尔茨海默氏症美国的疾病研究中心为国家阿尔茨海默氏症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成为最大的公开之一有关广告及相关疾病的可访问的神经病理数据集。在此提案中，我们将借鉴 Ann McKee博士，Dennis Dickson博士和John Crary博士的神经病理学专业知识 CTE，AGD和部分的调查。我们将使用152例AD和年龄相关的Tauopathies 波士顿大学，梅奥诊所杰克逊维尔和西奈山ADC识别新颖的tau和炎症标记以检测和区分疾病。我们还将确定CTE，部分，AGD和AGD的频率 NACC-ND中600个认知正常，轻度认知受损和痴呆的受试者中的ARTAG NACC-均匀数据集（UDS）诊断，并确定这些疾病对临床诊断的贡献以及认知和神经精神谱。我们将运用该项目获得的知识来开发CTE，一部分，AGD和ARTAG评估模块以及神经病理学上的临时标准与年龄相关的大疗法供一般使用。该建议将在研究中回答至关重要的需求神经变性。具体而言，它将在CTE，部分，AGD中识别新颖的Tau和神经炎症标记和Artag来帮助他们的发现和歧视。该项目还将确定这些项目的频率记忆障碍诊所患者中与年龄相关的调子病，并确定这些疾病是否存在有助于临床特征。此外，该项目将从 600例NACC病例（200个正常认知，200 MCI，200个痴呆症），具有UDS表型，可用于其他ADRC和NACC调查人员。这项研究有可能改变我们概念化的方式 MCI和痴呆症，最终通过发展协调而制定更有效的治疗策略诊断有助于临床诊断，认知和神经精神谱和记忆障碍患者的神经病理表型。