StressMarq’s Active Tau Proteins
StressMarq is excited to announce the launch of new active tau proteins to help researchers study tau aggregation, a hallmark of neurodegenerative diseases including Alzheimer’s. StressMarq is the first to offer active tau preformed fibrils (PFFs) and filaments for neuroscience research. The process of tau aggregation can be seeded by active tau PFFs, which recruit monomers to form larger tau fibrils. This has been demonstrated in thioflavin T assays where an increase in fluorescence, indicative of tau fibrillization, is seen when active tau PFFs are combined with active tau monomers. Certain tau PFFs have been injected into P301L mice, where they seed tau aggregation and induce tau pathology in the hippocampus.
Immunohistochemistry analysis of P301L mouse hippocampus injected with K18 P301L tau PFFs (SPR-330) shows seeding of tau pathology at injection site. AT8 (pSer202/pThr205) tau antibody shows tangle-like inclusions. Experiments performed at reMYND N.V.
Monomers and fibrils are available both in the full-length isoform of the tau protein (2N4R or Tau-441) or a truncated form (K18). Tau-441 has a molecular weight of approximately 46 kDa, whereas K18 tau has a molecular weight of approximately 15 kDa. dGAE is a fragment of the tau protein consisting of amino acids 297-391. It is one of the core PHF subunits,1 includes both microtubule-binding domains and proline-rich regions, and assembles into PHF-like fibrils in vitro without additives or templates.2
Proteins are available as wild-type or with a variety of mutations. P301S and P301L mutations occur in exon 10 and are associated with frontotemporal dementia. The P301S mutation reduces tau’s ability to assemble microtubules, and the P301L mutation promotes beta-sheet formation and the formation of PHFs. Both P301S and P301L mutant transgenic mouse models are used in tau research. The K280 deletion mutation is also associated with frontotemporal dementia and promotes fibrillization into paired helical filaments (PHFs) in the absence of heparin and other inducers. The C322A mutation also increases tau’s ability to form PHFs.2
PFFs induce tau aggregation; full-length PFFs may be more effective in seeding fibrillization, but a combination of both can be particularly toxic to neurons. Most tau varieties are fibrillized using a heparin scaffold; soluble tau filaments are fibrillized using a linear anionic scaffold. dGAE tau and K18 K280 deletion tau both fibrillize without scaffolds.
1. Novak, M. et al. (1993) EMBO J. 12, 365-370.
2. Al-Hilaly, Y.K. et al. (2017) J. Mol. Biol. 429(23):3650-3665.
StressMarq is in the process of developing new types of fibrils for neurodegenerative disease research as well as thoroughly characterizing our current products. We currently have several types of tau PFFs and filaments available. This table summarizes the differences between them: