Human brain single nucleus cell type enrichments in neurodegenerative diseases
Alvarado, C. X.; Weller, C. A.; Johnson, N. L.; Leonard, H. L.; Singleton, A. B.; Reed, X.; Blauewendraat, C.; Nalls, M. A.
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Single cell RNA sequencing has opened a window into clarifying the complex underpinnings of disease, particularly in quantifying the relevance of tissue- and cell-type-specific gene expression. To identify the cell types and genes important to therapeutic target development across the neurodegenerative disease spectrum, we leveraged genome-wide association studies, recent single cell sequencing data, and bulk expression studies in a diverse series of brain region tissues. We were able to identify significant immune-related cell types in the brain across three major neurodegenerative diseases: Alzheimers Disease, Amyotrophic Lateral Sclerosis, and Parkinsons Diseases. Subsequently, we identified the major role of 30 fine-mapped loci implicating seven genes in multiple neurodegenerative diseases and their pathogenesis.
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