Tau 1N4R (human, recombinant)

Tau is a member of the microtubule-associated protein (MAP) family that facilitates microtubule formation in axons.^1,2 It is primarily expressed in neurons and localized to axons, but trace amounts have been observed in glial cells and several peripheral tissues, including kidney, lung, and testis. Tau is composed of an N-terminal projection domain that interacts with neurofilaments, cytoplasmic organelles, and neuronal cell membranes and a C-terminal microtubule-binding domain that facilitates microtubule polymerization and stabilization. It is encoded by MAPT in humans, a 16-exon gene that produces six isoforms via alternative mRNA splicing, which differ from each other based on the presence of zero (0N), one (1N), or two (2N) inserts at the amino terminus and the number of microtubule-binding repeat (MTBR) domains at the C-terminus (3R or 4R for three and four repeats, respectively).³ Tau is subject to post-translational modifications, including phosphorylation, and hyperphosphorylation of tau is associated with the formation of neurofibrillary tangles and neuronal cell death in postmortem brains from patients with Alzheimer's disease.⁴ Mutations in MAPT lead to changes in expression of tau isoforms and the formation of insoluble protein aggregates that cause familial frontotemporal dementia (FTD) and parkinsonism linked to chromosome 17 (FTDP-17). Transgenic mice expressing wild-type human tau 1N4R exhibit motor and spatial memory impairments, and postmortem brain levels of insoluble tau 1N4R are increased in patients with Parkinson’s disease.^5,6

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1. Buée, L., Bussière, T., Buée-Scherrer, V., et al. Tau protein isoforms, phosphorylation and role in neurodegenerative disorders. Brain Res. Rev. 33(1), 95-130 (2000).

2. Arendt, T., Stieler, J.T., and Holzer, M. Tau and tauopathies. Brain Res. Bull. 126(Pt 3), 238-292 (2016).

3. Waheed, Z., Choudhary, J., Jatala, F.H., et al. The role of tau proteoforms in health and disease. Mol. Neurobiol. 60(9), 5155-5166 (2023).

4. Pîrşcoveanu, D.F.V., Pirici, I., Tudorică, V., et al. Tau protein in neurodegenerative diseases - a review. Rom. J. Morphol. Embryol. 58(4), 1141-1150 (2017).

5. Wheeler, J.M., McMillan, P.J., Hawk, M., et al. High copy wildtype human 1N4R tau expression promotes early pathological tauopathy accompanied by cognitive deficits without progressive neurofibrillary degeneration. Acta Neuropathol. Commun. 3, 33 (2015).

6. Tauber, C.V., Schwarz, S.C., Rösler, T.W., et al. Different MAPT haplotypes influence expression of total MAPT in postmortem brain tissue. Acta Neuropathol. Commun. 11(1), 40 (2023).