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ORIGINAL RESEARCH article

Front. Cell Dev. Biol.
Sec. Molecular and Cellular Pathology
Volume 12 - 2024 | doi: 10.3389/fcell.2024.1459573

Tau mediates the reshaping of the transcriptional landscape toward intermediate Alzheimer's disease stages

Provisionally accepted
Giacomo Siano Giacomo Siano 1,2*Martina Varisco Martina Varisco 2Marco Terrigno Marco Terrigno 3Congwei Wang Congwei Wang 3Marco Groth Marco Groth 4Marie-Christine Galas Marie-Christine Galas 5Jeroen Hoozemans Jeroen Hoozemans 6Alessandro Cellerino Alessandro Cellerino 2Antonino Cattaneo Antonino Cattaneo 2*Cristina Di Primio Cristina Di Primio 1*
  • 1 Istituto di Neuroscienze - CNR, Pisa, Italy
  • 2 Laboratory of Biology, Normal School of Pisa, Pisa, Tuscany, Italy
  • 3 Roche (Switzerland), Basel, Switzerland
  • 4 Leibniz Institute on Aging, Fritz Lipmann Institute (FLI), Jena, Thuringia, Germany
  • 5 INSERM UMR1172 Lille Neurosciences et Cognition, Lille, Nord-Pas-de-Calais, France
  • 6 Amsterdam Neuroscience, VU Medical Center, Amsterdam, Netherlands

The final, formatted version of the article will be published soon.

    Recent research revealed that Tau plays critical roles in various neuronal functions. We previously demonstrated that destabilization and nuclear delocalization of Tau alter the expression of glutamatergic genes, mediating early neuronal damage. In this study, we discovered that changes in Tau availability are linked to global alterations in gene expression that affect multiple neuronal pathways. Comparison with the human temporal region showed that the Tau-dependent modulation of gene expression closely resembles the intermediate stages of Alzheimer's disease (AD) that precede the definitive pathological condition. Furthermore, we identified the chromatin remodeling pathway as being significantly affected by Tau in both our cellular model and AD brains, with reductions inFormattato: Giustificato heterochromatin markers. Our findings indicate that Tau is able to globally affect the neuronal transcriptome and that its subcellular unbalance changes gene expression in the intermediate stages of AD development. In addition, we found that the epigenetic pathwaychromatin architecture is affected by Tau during the progression of AD. These results provide new insights into the molecular mechanisms underlying early stages of AD development and highlight the central role of Tau and the contribution of nuclear Tau in this process.

    Keywords: tau, Alzheimer's disease, Gene Expression, Chromatin remodeling, epigenetic markers, AD cellular model

    Received: 04 Jul 2024; Accepted: 01 Nov 2024.

    Copyright: © 2024 Siano, Varisco, Terrigno, Wang, Groth, Galas, Hoozemans, Cellerino, Cattaneo and Di Primio. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Giacomo Siano, Istituto di Neuroscienze - CNR, Pisa, Italy
    Antonino Cattaneo, Laboratory of Biology, Normal School of Pisa, Pisa, 56126, Tuscany, Italy
    Cristina Di Primio, Istituto di Neuroscienze - CNR, Pisa, Italy

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