Glial profiling of human tauopathy brain demonstrates enrichment of astrocytic transcripts in tau-related frontotemporal degeneration

• Type of Material: Article
• Authors: Ashlyn G Johnson, Emory University; James A Webster, Emory University; Chadwick Hales, Emory University
• Language: English
• Date: 2022-01-17
• Publisher: ELSEVIER SCIENCE INC
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2022 Elsevier Inc. All rights reserved.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.neurobiolaging.2021.12.005
• Title of Journal or Parent Work: NEUROBIOLOGY OF AGING
• Volume: 112
• Start Page: 55
• End Page: 73
• Grant/Funding Information: This work was supported by the National Institutes of Health [grant numbers P30AG066511 (Allan Levey), UL1TR002378]; NanoString Technologies [Glial Profiling Panel Grant at Emory University]; the BrightFocus Foundation (CMH); and discretionary funds (CMH).
• Keywords: DEMENTIA; LOBAR DEGENERATION; NEUROPATHOLOGY; Neurosciences; PHOSPHORYLATION; Neurosciences & Neurology; Tau; Life Sciences & Biomedicine; ALZHEIMERS; MUTATIONS; Frontotemporal degeneration; PROTEIN-TAU; DISEASE; COMPLEMENT; Science & Technology; Alzheimer's disease; Geriatrics & Gerontology; Astrocyte; Glia; EXPRESSION

Abstract

To understand how glia may be altered in frontotemporal degeneration with tau pathology (FTD-tau), we used a NanoString glial profiling panel to measure 770 transcripts related to glial biology in human control (n = 8), Alzheimer's disease (AD) (n = 8), and FTD-tau (n = 8) dorsolateral prefrontal cortex. Compared to control, 43 genes were upregulated and 86 genes were downregulated in the FTD-tau samples. Only 3 genes were upregulated and 2 were downregulated in AD. Pathway analysis revealed many astrocyte-, microglia-, and oligodendrocyte-related pathway scores increased in FTD-tau, while neuron-related pathway scores decreased. We compared these results to a previously published proteomic dataset containing many of the same samples and found that the targeted panel approach obtained measurements for genes whose proteins were not measured in the proteomics. Our results point to the utility of multiomic approaches and marked dysregulation of glia in FTD-tau.