Molecular Network Degeneration in FTLD-Related Pathology

痴呆症与微观和宏观神经元网络的选择性退化有关 导致临床特征的异质性。人类神经病理学和实验模型的数据 支持神经退行性疾病的病理通过选择性脆弱传播的假说 神经网络。额颞叶痴呆可在临床上表现为FTD的行为变异型(BvFTD)或 原发性进行性失语(PPA)。这两种临床表型都与积聚的 受影响脑区的蛋白质聚集物由TDP-43或tau蛋白组成。了解如何 额颞叶痴呆患者的神经网络退行性变对了解其进展具有重要意义 疾病，因为它涉及不同的临床和病理亚型。这个项目的目标是表演单曲 额叶退行性变关键区域的细胞RNA测序 识别因TDP-43和tau病理而特异改变的细胞水平的分子网络 行为变异型额颞叶痴呆和原发性进行性失语。新型生物信息学 方法将应用于scRNAseq数据集，以识别神经细胞类型和分子网络，这些网络 在额颞叶痴呆临床病理亚型中选择性易感。

Dementia is associated with selective degeneration of microscopic and macroscale neuronal networks resulting in heterogeneous clinical features. Data from human neuropathology and experimental models support the hypothesis that neurodegenerative disease pathologies spread through selectively vulnerable neuronal networks. Frontotemporal dementia can manifest clinically as behavioral variant of FTD (bvFTD) or primary progressive aphasia (PPA). Both clinical phenotypes can be associated with the accumulation of protein aggregates in affected brain regions composed of either TDP-43 or tau protein. Understanding how networks degenerate in fronototemporal dementia is important in terms of understanding the progression of disease as it relates to variable clinical and pathologic subtypes. The goal of this project is to perform single cell RNA sequencing (scRNAseq) of key regions that degenerate in frontotemporal lobar degeneration to identify cellular-level molecular networks that are specifically altered due to TDP-43 versus tau pathology in behavioral variant frontotemporal dementia and primary progressive aphasia. Novel bioinformatics approaches will be applied to scRNAseq datasets to identify neuronal cell types and molecular networks which are selectively vulnerable in frontotemporal dementia clinicopathologic subtypes.