Abstract
Tau is a microtubule-associated protein expressed in neuronal axons. Hyperphosphorylated tau is a major component of neurofibrillary tangles, a pathological hallmark of Alzheimer's disease (AD). Hyperphosphorylated tau aggregates are also found in many neurodegenerative diseases, collectively referred to as "tauopathies," and tau mutations are associated with familial frontotemporal lobar degeneration (FTLD). Previous studies have generated transgenic mice with mutant tau as tauopathy models, but nonhuman primates, which are more similar to humans, may be a better model to study tauopathies. For example, the common marmoset is poised as a nonhuman primate model for investigating the etiology of age-related neurodegenerative diseases. However, no biochemical studies of tau have been conducted in marmoset brains. Here, we investigated several important aspects of tau, including expression of different tau isoforms and its phosphorylation status, in the marmoset brain. We found that marmoset tau does not possess the "primate-unique motif" in its N-terminal domain. We also discovered that the tau isoform expression pattern in marmosets is more similar to that of mice than that of humans, with adult marmoset brains expressing only four-repeat tau isoforms as in adult mice but unlike in adult human brains. Of note, tau in brains of marmoset newborns was phosphorylated at several sites associated with AD pathology. However, in adult marmoset brains, much of this phosphorylation was lost, except for Ser-202 and Ser-404 phosphorylation. These results reveal key features of tau expression and phosphorylation in the marmoset brain, a potentially useful nonhuman primate model of neurodegenerative diseases.
Highlights
Tau is a microtubule-associated protein expressed in neuronal axons
We cloned tau cDNA from cDNA libraries of marmoset brains on postnatal day 0 (P0) and of adults (23 months) using 5Ј and 3Ј primers based on the predicted DNA sequence by PCR. 0N3R tau cDNA with no N-terminal insertion and three MTB repeats (3R) was isolated from the cDNA library of a newborn marmoset brain, and 0N4R (no N-terminal insertion and four MTB repeats (4R)) and 2N4R were obtained from that of an adult marmoset brain
The similar results were obtained from another set of primers (Fig. S3). These results indicate that the isoforms of 0N3R and, to a lesser extent, 0N4R tau are expressed in the brains of newborn marmosets, whereas those of 0N4R and 2N4R are expressed in adult marmoset brains at the mRNA level
Summary
The immunostaining of NFTs with several anti-phospho-tau antibodies is routinely employed to provide a final diagnosis of AD or other tauopathies [12, 13], but the significance of tau phosphorylation for the development of AD or tauopathies is not yet clear This is because of the difficulty of studying the phosphorylation states of tau in human brains. Rodents have alternatively been used for the analysis of in vivo tau phosphorylation [8, 19, 20] They might have provided useful information implicating the phosphorylation of tau in human brains, but there are arguments that rodents do not necessarily serve as a proper model of tauopathies, which develop in aged individuals. We isolated tau cDNA from marmoset brains and investigated the expression of tau isoforms and phosphorylation, two important properties of tau related to AD pathology. We found that marmoset tau resembled mouse tau more than human tau in isoform expression
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
