Home General Physiology and Biophysics 2021 General Physiology and Biophysics Vol.40, No.6, p.541–549, 2021

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Founded: 1982
ISSN  1338-4325 (online)

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General Physiology and Biophysics Vol.40, No.6, p.541–549, 2021

Title: Transcriptomic signature of Alzheimer’s disease tau seed-induced pathology
Author: Nikoleta Csicsatkova, Peter Szalay, Katarina Matyasova, Veronika Mate, Martin Cente, Tomas Smolek, Veronika Brezovakova, Lucie Kawecka, Norbert Zilka, Santosh Jadhav

Abstract: Spreading of tau pathology to anatomical distinct regions in Alzheimer’s disease (AD) is associated with progression of the disease. Studies in recent decade have strived to understand the processes involved in this characteristic spread. We recently showed that AD-derived insoluble tau seeds are able to initiate neurofibrillary pathology in transgenic rodent model of tauopathy. In the present study, we pursued to identify the molecular changes that govern the induction and propagation of tau pathology on the transcriptomic level. We first show that microglia in vicinity to AD-Tau-induced pathology has phagocytic morphology when compared to PBS-injected group. On transcriptomic level, we observed deregulation of 15 genes 3-month post AD-Tau seeds inoculation. Integrated bioinformatic analysis identified 31 significantly enriched pathways. Amongst these, the inflammatory signalling pathway mediated by cytokine and chemokine networks, along with, toll-like receptor and JAK-STAT signalling were the most dominant. Furthermore, the enriched signalling also involved the regulation of autophagy, mitophagy and endoplasmic reticulum stress pathways. To our best of knowledge, the study is the first to investigate the transcriptomic profile of AD-Tau seed-induced pathology in hippocampus of transgenic model of tauopathy.

Keywords: Alzheimer’s disease — Tau spreading — Misfolded tau — Gene expression — Microglia
Published online: 30-Nov-2021
Year: 2021, Volume: 40, Issue: 6 Page From: 541, Page To: 549

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