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Molecular Network Degeneration in FTLD-Related Pathology

FTLD 相关病理学中的分子网络变性

基本信息

批准号：
10454269
负责人：
Edward Byung-Ha Lee
金额：
$ 28.36万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-15 至 2025-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10454269
关键词：
Affect Aging Algorithms Anatomy Anterior Area Autopsy Biochemistry Bioinformatics Biometry Biostatistics Core Brain Brain region Cells Cellular biology Cessation of life Clinical Complex Data Data Set Dementia Disease Disease Progression Experimental Models Frontotemporal Dementia Frontotemporal Lobar Degenerations Gene Expression Genetic Goals Heterogeneity Human Immunohistochemistry Individual Inferior Knowledge Language Lead Ligands Methods Microscopic Molecular Network-based Neurodegenerative Disorders Neurologic Neurons Nodal Onset of illness Pathologic Pathology Phenotype Primary Progressive Aphasia Resources Series Stereotyping Syndrome System Temporal Lobe Testing Tissues Variant base behavioral variant frontotemporal dementia brain tissue cell type cingulate gyrus clinical heterogeneity clinical phenotype design frontal lobe frontotemporal degeneration graph theory grasp human RNA sequencing human data human disease improved molecular phenotype neocortical neuropathology novel protein TDP-43 protein aggregation receptor single-cell RNA sequencing tau Proteins transcriptome sequencing

项目摘要

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.

痴呆症与微观和宏观神经网络的选择性变性有关