<p>This data is the first part of a larger single cell and tissue level functional genomics analysis of dementias with tau pathology.  Cellular resolution will clarify the role of glial genes and pathways in neurodegenerative disease.  This includes understanding the role of microglia and astrocytes in neurodegenerative disorders characterized by Tau protein pathology.  To achieve a refined view of microglial neuroinflammatory signaling in tau-associated neurodegeneration, we performed a functional genomic analysis that integrated time-course gene expression data from mouse models expressing human mutant MAPT (the tau gene) with single nuclear sequencing data obtained from patients with frontotemporal dementia with Tau protein pathology (Pick’s disease).    This included microglia-specific gene expression data obtained from single nuclear sequencing of postmortem frozen precentral gyrus samples collected from 16 total individuals, including 8 subjects with clinical diagnosis of behavior variant frontotemporal dementia and neuropathological diagnosis of Pick’s disease (Tau protein pathology) and controls (n=8).  Our findings present detailed molecular profiles of disease-associated microglial transitions over the course of tau-associated neurodegeneration.  Furthermore, we demonstrate overlap between microglia profiles obtained from precentral gyrus of patients with Pick’s disease with those up-regulated during the neurodegenerative stage in mice expressing human MAPT mutations.</p>

Single Cell and Tissue Level Functional Genomics Analysis of Astrocyte-Related Mechanisms in Taupathy