Clinical, Neuroanatomic, and Pathologic Signatures of FTLD-tau in Dementia Phenotypes - Diversity Supplement

额颞部 品种 脑叶变性I S，尸检中发现的一种神经退行性疾病 在临床痴呆综合征中，是65岁以下痴呆症的第二大常见原因[1]。 患有FTLD相关痴呆的患者得不到足够的服务，部分原因是 痴呆症和潜在的病理还没有被很好地理解。复杂性很大程度上在于这样一个事实，即相同的 病理学 引起 痴呆症 可以导致不同的痴呆症综合症，反之，单一的痴呆症综合症可以 由多种病理因素造成的。这项提议的目标是理清两者之间的复杂关系 症状、解剖萎缩、细胞死亡和一种特殊形式的FTLD，称为FTLD-taa。 因此，这项工作将有助于确定FTLD-tau中可能的神经退行性变的底物。 这项研究集中在显示最常见形式的死后人类样本的强大队列中 FTLD-tau：Pick病、皮质基底膜变性(CBD)和进行性核上性瘫痪(PSP)。这些 肌萎缩侧索硬化症是原发疾病的基础 渐进式 综合征 单纯性肌萎缩侧索硬化症(皮克氏病)的细胞特征 症状： 痴呆症 型号 将要 案例 体视学 临床 中区 显示 高ppa和bvFTD， 具体地说，为探索解剖学的组织和病理靶点提供令人兴奋的机会 神经退行性疾病中的网络。这项多学科研究的结果将澄清 进行性失语(PPA)是一种临床痴呆综合征，其特征是 临床痴呆--L变异型额颞叶痴呆的语言和行为障碍 以行为方式的渐进式变化为特点。目标1将决定 不同类型痴呆症的生前诊断6例 PPA(PPA-S和PPA-G)和bvFTD的语义和语法变体。这些 每个症状都与不同的萎缩模式和临床特征有关，提供了一个理想的 探索负责认知或行为的解剖区域的选择性脆弱性。目标2 通过研究Pick‘s病、CBD和PSP的多种病理变化来研究两者之间的反向关系 死前诊断为单一痴呆综合征(PPA-G或bvFTD)。组织学上的和公正的 方法将被用来确定FTLD-tau病理之间的关系，而不仅仅是详细 不仅与神经元、神经胶质细胞和突触的异常有关，而且还与MRI的定量萎缩模式有关。一个 他工作的假设是FTLD-tau和相关细胞特征的区域分布将 与萎缩的解剖模式和不同的临床特征相一致。 这是旨在建立临床、解剖和病理上的一致性的首批同类工作之一。 临床痴呆症和引起痴呆的神经官能症之间的特异性。 具体目标和 ( 病理性的 支持痴呆的临床异质性，加深我们对选择性治疗原则的理解 易损害性，与开发专门针对脊椎病的诊断工具和治疗方法高度相关。

Frontotemporal variety lobar degeneration (FTLD) i s a neurodegenerative disease found at autopsy that underlies a of clinical dementia syndromes, and is the second most common cause of dementia under age 65 [1]. Patients with FTLD-related dementias are underserved in part because the complex relationship between dementias and underlying pathology is not well understood. Much of the complexity lies in the fact that the same pathology caused dementia can cause different dementia syndromes and, conversely, that a single dementia syndrome can be by multiple pathologies. T he goal of this proposal is to disentangle the complex relationship between syndromes, anatomic atrophy, cell death, and a specific form of FTLD, known as FTLD-tau.In doing so, this work will help identify the putative substrates of neurodegeneration in FTLD-tau. This study focuses on a robust cohort of postmortem human specimens that show the most common forms of FTLD-tau: Pick's disease, corticobasal degeneration (CBD), and progressive supranuclear palsy (PSP). These tauopathies can underlie primary progressive syndrome cellular features of a single tauopathy (Pick's disease) in syndromes: dementia model will cases stereological clinical central show high PPA and bvFTD, specifically, offer exciting opportunities for exploring the organization and pathologic targets of anatomic networks in neurodegenerative diseases. Outcomes of this multidisciplinary study will clarify progressive aphasia (PPA), a clinical dementia syndrome characterized by language impairment, and behaviora l variant frontotemporal dementia (bvFTD), a clinical dementia characterized by progressive changes in comportment. Aim 1 will determine the cases diagnosed antemortem with different dementia the semantic and agrammatic variants of PPA (PPA-S and PPA-G, respectively) and bvFTD. These syndromes are each associated with distinct patterns of atrophy and clinical profiles, providing an ideal to explore the selective vulnerabilities of anatomic regions responsible for cognition or behavior. Aim 2 study the converse relationship by investigating multiple pathologies Pick's disease, CBD, and PSP) in diagnosed antemortem with a single dementia syndrome (PPA-G or bvFTD). Histological and unbiased methods will be used to determine relationships between FTLD-tau pathology, not only to detailed profiles and quantitative MRI atrophy patterns, but also to neuronal, glial, and synaptic abnormalities. A hypothesis of t his work is that regional distributions of FTLD-tau — and related cellular features — will concordance with anatomic patterns of atrophy and distinct clinical profiles. This is one of the first works of its kind that aims to establish clinical, anatomic, and pathologic concordance of specificity between clinical dementia syndromes and the tauopathies that cause them. specific targets and ( the pathologic underpinningsof clinical heterogeneity in dementias,sharpen our understanding of the principles of selective vulnerability, and are highly relevant for the development of tauopathy-specific diagnostic tools and treatments.