Instituto Universitario de Biología Molecular

Tau function and dysfunctions in Alzheimer disease

  • Félix Hernández Pérez. Profesor Titular. Departamento de Biología Molecular. UAM.

(Co-PI with Dr. Jesús Avila, CSIC-CBMSO)

  • Vega García-Escudero. Profesora Contratada Doctora Interina. Departamento de Anatomía, Histología y Neurociencias. UAM.


Tau is mainly a neuronal protein that could be involved in several cellular functions in addition of being a microtubule associated protein. At the present, we are analyzing those functions and we continue with the study of the possible role of tau in Alzheimer disease (AD) and other tauopathies. During 2021-2022, we have tested: a) the presence of tau in non-neuronal cells, b) the presence of new tau isoform and c) we have started to look for a possible specific role of tau in neuronal aging, since aging is the main risk factor for Alzheimer disease.

About the presence of tau in non-neuronal cells, we have found that tau could be present in microglia cells, being that presence the consequence of the endocytosis of extracellular (neuronal) tau into microglia cells. Also, we have found that the effect of tau in microglia cells results in the activation of p38 kinase that could be toxic for the cell. In that way, inhibition of p38 kinase decreases tau toxicity in microglia cells and improves microglia phagocytic function. Additionally, tau expression was found in kidney cells playing, this kidney tau, a role in podocyte architecture.

A new tau isoform raised by intron 12 retention has been described. This new tau isoform contains an extra 16aa peptide, only present in humans, with two tryptophan residues and we named it as W-Tau isoform. Looking at W-Tau isoform, we have found that it has a low capacity for self-aggregation, unlike of the previously known human tau isoforms. Also, W-Tau isoform could prevent the aggregation of the other tau isoforms. In vitro experiments, using the 16aa peptide, specific for W-Tau, have indicated that such peptide could prevent not only tau self-assembly but also beta amyloid peptide aggregation.

During this period, we have studied aging at the dentate gyrus (DG) and hippocampal region of old mice, since DG is one of the regions that are earlier affected in AD. Previously, we described, in vivo, that aging features in DG from old mice could be ameliorated expressing the so-called Yamanaka Factors (YF). Now, we are looking for more simple factors that could replace the action of YF and starting to look for a specific tau function in neuronal aging.

Finally, our group has done several collaborations, located inside and outside of the CBMSO, in aspects related to Alzheimer disease and other neurodegenerative disorders like aging.