Transcriptomic signature of Alzheimer's disease tau seed-induced pathology

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.

Automated summary

This study is the first to investigate the transcriptomic profile of AD-Tau seed-induced pathology in the hippocampus of a transgenic tauopathy model. The research identified molecular changes and inflammatory signaling pathways, as well as pathways related to autophagy and endoplasmic reticulum stress that may play crucial roles in the induction and propagation of tau pathology.