Rat tau proteome consists of six tau isoforms: implication for animal models of human tauopathies

Abstract

Human brain encompasses six tau isoforms, containing either three (3R) or four (4R) repeat domains, all of which participate in the pathogenesis of human tauopathies. To investigate the role of tau protein in the disease, transgenic rat models have been created. However, unlike humans, it has been suggested that rat brain expresses only three 4R tau isoforms. Because of the significance of the number of tau isoforms for faithful reproducibility of neurofibrillary pathology in transgenic rat models, we reopened this issue. Surprisingly, our results showed that adult rat brain contains six tau isoforms like humans. Protein expression of 4R tau isoforms was ninefold higher than 3R isoforms. Furthermore, the protein levels of tau isoforms with none, one or two N-terminal inserts were 30%, 35%, and 35% of total tau, respectively. Moreover, amount and ratio of tau isoforms were developmentally regulated. The levels of 4R tau isoforms progressively increased from early postnatal period until adulthood, whereas the expression of 3R tau isoforms reached maximum at P10 and then gradually declined. Our results show that rat brain encompasses full tau proteome similar to humans. These findings support the use of rat as an animal model in human tauopathies research.

Protein aggregate formation in oligodendrocytes: tau and the cytoskeleton at the intersection of neuroprotection and neurodegeneration

“…It has been implied that in adult rodent brain only 4R-tau isoforms are expressed. However, our data demonstrated that in rat brain 3R-tau isoforms are present yet at a much lower level (Müller et al, 1997;Gorath et al, 2001), which was later corroborated by Hanes et al (2009). In cultured oligodendrocytes tau protein is developmentally regulated and 4R-isoforms become more prominent, while 3R-isoforms decrease (Seiberlich et al, 2015).…”

Truncation and Activation of Dual Specificity Tyrosine Phosphorylation-regulated Kinase 1A by Calpain I

“…7, A and B). Rodent brain mainly expresses 4R-Tau and only very little 3R-Tau (58). We investigated the levels of Tau in the KA-induced excitotoxic brain.…”

Polymeric alkylpyridinium salts permit intracellular delivery of human Tau in rat hippocampal neurons: requirement of Tau phosphorylation for functional deficits

“…Especially for the investigation of Tau, rats express not only the 4R Tau isoforms of mice [47], but also the 3R isoforms in adulthood [48] akin to the human proteome [49]. Such human homology may be of critical importance when modelling certain aspects of tauopathies given the putative differences in pathological processing of 3R or 4R isoforms of Tau [49].…”