Key Spec Table
|Species Reactivity||Key Applications||Host||Format||Antibody Type|
|H||DB, ELISA, IF, IHC, IP, NEUT, WB||Rb||Serum||Polyclonal Antibody|
|Presentation||Rabbit polyclonal serum containing 0.02% sodium azide.|
|Safety Information according to GHS|
|Material Size||100 µL|
Anti-Tau (T22), oligomeric Antibody SDS
|Anti-PHOX2A Polyclonal Antibody||VP1807254|
|Anti-Tau (T22), Oligomeric - 2930198||2930198|
|Anti-Tau (T22), Oligomeric - 3182604||3182604|
|Anti-Tau (T22), Oligomeric - 3352007||3352007|
|Anti-Tau (T22), Oligomeric -2702136||2702136|
|Anti-Tau (T22), Oligomeric -2730017||2730017|
|Anti-Tau (T22), Oligomeric -2776621||2776621|
|Anti-Tau (T22), Oligomeric -2798560||2798560|
|Anti-Tau (T22), Oligomeric -2854163||2854163|
|Anti-Tau (T22), Oligomeric Polyclonal Antibody||3055586|
|Reference overview||Application||Species||Pub Med ID|
|Small misfolded Tau species are internalized via bulk endocytosis and anterogradely and retrogradely transported in neurons.|
Wu, JW; Herman, M; Liu, L; Simoes, S; Acker, CM; Figueroa, H; Steinberg, JI; Margittai, M; Kayed, R; Zurzolo, C; Di Paolo, G; Duff, KE
The Journal of biological chemistry 288 1856-70 2013
The accumulation of Tau into aggregates is associated with key pathological events in frontotemporal lobe degeneration (FTD-Tau) and Alzheimer disease (AD). Recent data have shown that misfolded Tau can be internalized by cells in vitro (Frost, B., Jacks, R. L., and Diamond, M. I. (2009) J. Biol. Chem. 284, 12845-12852) and propagate pathology in vivo (Clavaguera, F., Bolmont, T., Crowther, R. A., Abramowski, D., Frank, S., Probst, A., Fraser, G., Stalder, A. K., Beibel, M., Staufenbiel, M., Jucker, M., Goedert, M., and Tolnay, M. (2009) Nat. Cell Biol. 11, 909-913; Lasagna-Reeves, C. A., Castillo-Carranza, D. L., Sengupta, U., Guerrero-Munoz, M. J., Kiritoshi, T., Neugebauer, V., Jackson, G. R., and Kayed, R. (2012) Sci. Rep. 2, 700). Here we show that recombinant Tau misfolds into low molecular weight (LMW) aggregates prior to assembly into fibrils, and both extracellular LMW Tau aggregates and short fibrils, but not monomers, long fibrils, nor long filaments purified from brain extract are taken up by neurons. Remarkably, misfolded Tau can be internalized at the somatodendritic compartment, or the axon terminals and it can be transported anterogradely, retrogradely, and can enhance tauopathy in vivo. The internalized Tau aggregates co-localize with dextran, a bulk-endocytosis marker, and with the endolysosomal compartments. Our findings demonstrate that exogenous Tau can be taken up by cells, uptake depends on both the conformation and size of the Tau aggregates and once inside cells, Tau can be transported. These data provide support for observations that tauopathy can spread trans-synaptically in vivo, via cell-to-cell transfer.
|Rapid accumulation of endogenous tau oligomers in a rat model of traumatic brain injury: possible link between traumatic brain injury and sporadic tauopathies.|
Hawkins, BE; Krishnamurthy, S; Castillo-Carranza, DL; Sengupta, U; Prough, DS; Jackson, GR; DeWitt, DS; Kayed, R
The Journal of biological chemistry 288 17042-50 2013
Traumatic brain injury (TBI) is a serious problem that affects millions of people in the United States alone. Multiple concussions or even a single moderate to severe TBI can also predispose individuals to develop a pathologically distinct form of tauopathy-related dementia at an early age. No effective treatments are currently available for TBI or TBI-related dementia; moreover, only recently has insight been gained regarding the mechanisms behind their connection. Here, we used antibodies to detect oligomeric and phosphorylated Tau proteins in a non-transgenic rodent model of parasagittal fluid percussion injury. Oligomeric and phosphorylated Tau proteins were detected 4 and 24 h and 2 weeks post-TBI in injured, but not sham control rats. These findings suggest that diagnostic tools and therapeutics that target only toxic forms of Tau may provide earlier detection and safe, more effective treatments for tauopathies associated with repetitive neurotrauma.
|Accelerated neurodegeneration through chaperone-mediated oligomerization of tau.|
Blair, LJ; Nordhues, BA; Hill, SE; Scaglione, KM; O'Leary, JC; Fontaine, SN; Breydo, L; Zhang, B; Li, P; Wang, L; Cotman, C; Paulson, HL; Muschol, M; Uversky, VN; Klengel, T; Binder, EB; Kayed, R; Golde, TE; Berchtold, N; Dickey, CA
The Journal of clinical investigation 123 4158-69 2013
Aggregation of tau protein in the brain is associated with a class of neurodegenerative diseases known as tauopathies. FK506 binding protein 51 kDa (FKBP51, encoded by FKBP5) forms a mature chaperone complex with Hsp90 that prevents tau degradation. In this study, we have shown that tau levels are reduced throughout the brains of Fkbp5-/- mice. Recombinant FKBP51 and Hsp90 synergized to block tau clearance through the proteasome, resulting in tau oligomerization. Overexpression of FKBP51 in a tau transgenic mouse model revealed that FKBP51 preserved the species of tau that have been linked to Alzheimer's disease (AD) pathogenesis, blocked amyloid formation, and decreased tangle load in the brain. Alterations in tau turnover and aggregate structure corresponded with enhanced neurotoxicity in mice. In human brains, FKBP51 levels increased relative to age and AD, corresponding with demethylation of the regulatory regions in the FKBP5 gene. We also found that higher FKBP51 levels were associated with AD progression. Our data support a model in which age-associated increases in FKBP51 levels and its interaction with Hsp90 promote neurotoxic tau accumulation. Strategies aimed at attenuating FKBP51 levels or its interaction with Hsp90 have the potential to be therapeutically relevant for AD and other tauopathies.
|Identification of oligomers at early stages of tau aggregation in Alzheimer's disease.|
Lasagna-Reeves, CA; Castillo-Carranza, DL; Sengupta, U; Sarmiento, J; Troncoso, J; Jackson, GR; Kayed, R
FASEB journal : official publication of the Federation of American Societies for Experimental Biology 26 1946-59 2012
Neurofibrillary tangles (NFTs) are a pathological hallmark of Alzheimer's disease (AD); however, the relationship between NFTs and disease progression remains controversial. Analyses of tau animal models suggest that phenotypes coincide with accumulation of soluble aggregated tau species but not the accumulation of NFTs. The pathological role of prefilamentous tau aggregates, e.g., tau oligomeric intermediates, is poorly understood, in part because of methodological challenges. Here, we engineered a novel tau oligomer-specific antibody, T22, and used it to elucidate the temporal course and biochemical features of oligomers during NFT development in AD brain. We found that tau oligomers in human AD brain samples were 4-fold higher than those in the controls. We also revealed the role of oligomeric tau conformers in pretangles, neuritic plaques, and neuropil threads in the frontal cortex tissue from AD brains; this analysis uncovers a consistent code that governs tau oligomerization with regard to degree of neuronal cytopathology. These data are the first to characterize the role of tau oligomers in the natural history of NFTs, and they highlight the suitability of tau oligomers as therapeutic targets in AD and related tauopathies.
|Alzheimer brain-derived tau oligomers propagate pathology from endogenous tau.|
Lasagna-Reeves, CA; Castillo-Carranza, DL; Sengupta, U; Guerrero-Munoz, MJ; Kiritoshi, T; Neugebauer, V; Jackson, GR; Kayed, R
Scientific reports 2 700 2012
Intracerebral injection of brain extracts containing amyloid or tau aggregates in transgenic animals can induce cerebral amyloidosis and tau pathology. We extracted pure populations of tau oligomers directly from the cerebral cortex of Alzheimer disease (AD) brain. These oligomers are potent inhibitors of long term potentiation (LTP) in hippocampal brain slices and disrupt memory in wild type mice. We observed for the first time that these authentic brain-derived tau oligomers propagate abnormal tau conformation of endogenous murine tau after prolonged incubation. The conformation and hydrophobicity of tau oligomers play a critical role in the initiation and spread of tau pathology in the naïve host in a manner reminiscent of sporadic AD.