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变性有关 导致不同的临床特征。来自人类神经病理学和实验模型的数据 支持神经退行性疾病病理通过选择性脆弱的 神经网络额颞叶痴呆在临床上表现为FTD的行为变体（bvFTD）或 原发性进行性失语（PPA）。两种临床表型都可能与 在受影响的脑区域中的蛋白质聚集体由TDP-43或tau蛋白组成。了解如何 在额颞叶痴呆中网络退化对于理解 疾病，因为它涉及可变的临床和病理亚型。这个项目的目标是执行单一的 细胞RNA测序（scRNAseq）的关键区域，退化的额颞叶变性， 鉴定由于TDP-43相对于tau病理学而特异性改变的细胞水平分子网络， 行为变异性额颞叶痴呆和原发性进行性失语症。新生物信息学 这些方法将应用于scRNAseq数据集，以识别神经元细胞类型和分子网络， 在额颞叶痴呆临床病理亚型中选择性地脆弱。

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.