Human brain single nucleus cell type enrichments in neurodegenerative diseases

medRxiv [Preprint]. 2023 Jul 1:2023.06.30.23292084. doi: 10.1101/2023.06.30.23292084.

Abstract

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: Alzheimer's Disease, Amyotrophic Lateral Sclerosis, and Parkinson's Diseases. Subsequently, we identified the major role of 30 fine-mapped loci implicating seven genes in multiple neurodegenerative diseases and their pathogenesis.

Keywords: Alzheimer’s Disease; Amyotrophic Lateral Sclerosis; Frontotemporal Dementia Lobar Degeneration; Lewy Body Dementia; MAGMA; Neurodegeneration; Parkinson’s Disease; Progressive supranuclear palsy; colocalization; single cell expression.

Publication types

  • Preprint