p(HBP:"Tau epitope, AT8")

Entity

Name

Tau epitope, AT8

Namespace

HBP

Namespace Version

20190207

Namespace URL

https://raw.githubusercontent.com/pharmacome/terminology/cf4d8bb88754f036b943b4d94ad96e103dcb7149/export/hbp-names.belns

The pSer422 antibody displayed an almost identical pattern to that of AT8, in that it stained NFTs (Figure 5A–D), neuropil threads and neuritic plaques (Figure 5E–H) PubMed:18239272

The pSer422 antibody displayed an almost identical pattern to that of AT8, in that it stained NFTs (Figure 5A–D), neuropil threads and neuritic plaques (Figure 5E–H) PubMed:18239272

Hence, LTD-inducing NMDA receptor activation leads to an increase in tau phosphorylation at sites PHF-1, AT180, as well as AT8 and to a reduction at AT100. PubMed:22833681

Phosphorylation at the epitope Ser202/Thr205 is regarded as a good marker for late-stage NFTs (5, 72). Hyman and colleagues (5) demonstrated that AT8 immunoreactivity is present primarily in eNFTs and in certain cases in iNFTs. These investigators also found that AT8 revealed dense neuropil thread staining. PubMed:22253473

QA appears to act through NMDA receptor activation similar to other agonists, glutamate and NMDA and was abrogated by the NMDAR antagonist memantine. NMDA receptor agonists, glutamate and NMDA at equimolar concentrations (500 nM) increased tau phosphorylation at serine 199/202 (AT8) and threonine 231 (AT-180), similar to QA. PubMed:19623258

Because S199/S202/T205E, S396/S404E, 6-Phos and 7-Phos all demonstrated an AD-like shift in mobility as a result of phosphorylation-like changes, we conclude that they have the characteristics of hyperphosphorylated tau. These mutants will therefore be referred to as pseudo-hyperphosphorylated tau throughout the manuscript. On the basis of the observations that pseudohyperphosphorylated tau has decreased affinity for microtubules and reduced inducer-initiated rates of nucleation and polymerization, we propose that this combination could be the cause of the increased cytotoxicity of hyperphosphorylated tau in Alzheimer's disease and also explain the potentially beneficial role of tau polymerization and NFT formation. PubMed:19459590

We demonstrated that the treatment of cultured hippocampal neurons with 125 µM glutamate for 20 min induced the cleavage of p35 to produce the p25 fragment 6 h after glutamate treatment, and the maximal levels of p25 were detected at 12 h (Fig. 1A), which is consistent with a peak in tau hyperphosphorylation (AT8). PubMed:27087442

Because S199/S202/T205E, S396/S404E, 6-Phos and 7-Phos all demonstrated an AD-like shift in mobility as a result of phosphorylation-like changes, we conclude that they have the characteristics of hyperphosphorylated tau. These mutants will therefore be referred to as pseudo-hyperphosphorylated tau throughout the manuscript. On the basis of the observations that pseudohyperphosphorylated tau has decreased affinity for microtubules and reduced inducer-initiated rates of nucleation and polymerization, we propose that this combination could be the cause of the increased cytotoxicity of hyperphosphorylated tau in Alzheimer's disease and also explain the potentially beneficial role of tau polymerization and NFT formation. PubMed:19459590

Using mass spectrometry, we identified multiple sites on recombinant tau that are phosphorylated by LRRK2 in vitro, including pT149 and pT153, which are phospho-epitopes that to date have been largely unexplored. Importantly, we demonstrate that expression of transgenic LRRK2 in a mouse model of tauopathy increased the aggregation of insoluble tau and its phosphorylation at T149, T153, T205, and S199/S202/T205 epitopes. PubMed:24113872

Thus, the increase in ac-tau induced by SIRT1 deficiency is accompanied by accumulation of pathogenic p-tau in primary neurons. In mouse brains, deleting SIRT1, which elevated ac-tau, also increased AT8-positive p-tau. PubMed:20869593

Thus, the increase in ac-tau induced by SIRT1 deficiency is accompanied by accumulation of pathogenic p-tau in primary neurons. In mouse brains, deleting SIRT1, which elevated ac-tau, also increased AT8-positive p-tau. PubMed:20869593

Tau peptides containing phosphorylated S202, T205, and T396 were found only in Tg mice, supporting our results using AT8 and PHF1 antibodies PubMed:14642273

CRF-OE mice had significantly elevated tau-P compared to wild type (WT) mice at the AT8 (S202/T204), PHF-1 (S396/404), S262, and S422 sites. Treating CRF-OE mice with R121919 blocked phosphorylation at the AT8 (S202/T204) and PHF-1 (S396/404) sites, but not at the S262 and S422 sites and reduced phosphorylation of c-Jun N Terminal Kinase (JNK). PubMed:25125464

CRF-OE mice had significantly elevated tau-P compared to wild type (WT) mice at the AT8 (S202/T204), PHF-1 (S396/404), S262, and S422 sites. Treating CRF-OE mice with R121919 blocked phosphorylation at the AT8 (S202/T204) and PHF-1 (S396/404) sites, but not at the S262 and S422 sites and reduced phosphorylation of c-Jun N Terminal Kinase (JNK). PubMed:25125464

Analysis of synaptosomes revealed that FynCA accumulated at high levels in the spine, resulting in increased levels of the NMDA receptor subunit NR2b phosphorylated at residue Y1472. Tau was strongly phosphorylated at the AT8 epitope S202/T205 as shown by Western blot and immunohistochemistry indicating that an increased tyrosine kinase activity of Fyn has down-stream consequences for serine/threonine-directed phosphorylation. PubMed:25125464

The pSer422 antibody displayed an almost identical pattern to that of AT8, in that it stained NFTs (Figure 5A–D), neuropil threads and neuritic plaques (Figure 5E–H) PubMed:18239272

Indeed, Tau phosphorylation at the three positions, Ser202/Thr205/Ser208, while not at Ser262, is sufficient to induce aggregation without the addition of any exogenous aggregation inducer. PubMed:28784767

The pSer422 antibody displayed an almost identical pattern to that of AT8, in that it stained NFTs (Figure 5A–D), neuropil threads and neuritic plaques (Figure 5E–H) PubMed:18239272

The pSer422 antibody displayed an almost identical pattern to that of AT8, in that it stained NFTs (Figure 5A–D), neuropil threads and neuritic plaques (Figure 5E–H) PubMed:18239272

The pSer422 antibody displayed an almost identical pattern to that of AT8, in that it stained NFTs (Figure 5A–D), neuropil threads and neuritic plaques (Figure 5E–H) PubMed:18239272

Indeed, Tau phosphorylation at the three positions, Ser202/Thr205/Ser208, while not at Ser262, is sufficient to induce aggregation without the addition of any exogenous aggregation inducer. PubMed:28784767

We demonstrated that the treatment of cultured hippocampal neurons with 125 µM glutamate for 20 min induced the cleavage of p35 to produce the p25 fragment 6 h after glutamate treatment, and the maximal levels of p25 were detected at 12 h (Fig. 1A), which is consistent with a peak in tau hyperphosphorylation (AT8). PubMed:27087442

CRF-OE mice had significantly elevated tau-P compared to wild type (WT) mice at the AT8 (S202/T204), PHF-1 (S396/404), S262, and S422 sites. Treating CRF-OE mice with R121919 blocked phosphorylation at the AT8 (S202/T204) and PHF-1 (S396/404) sites, but not at the S262 and S422 sites and reduced phosphorylation of c-Jun N Terminal Kinase (JNK). PubMed:25125464

Because S199/S202/T205E, S396/S404E, 6-Phos and 7-Phos all demonstrated an AD-like shift in mobility as a result of phosphorylation-like changes, we conclude that they have the characteristics of hyperphosphorylated tau. These mutants will therefore be referred to as pseudo-hyperphosphorylated tau throughout the manuscript. On the basis of the observations that pseudohyperphosphorylated tau has decreased affinity for microtubules and reduced inducer-initiated rates of nucleation and polymerization, we propose that this combination could be the cause of the increased cytotoxicity of hyperphosphorylated tau in Alzheimer's disease and also explain the potentially beneficial role of tau polymerization and NFT formation. PubMed:19459590

Because S199/S202/T205E, S396/S404E, 6-Phos and 7-Phos all demonstrated an AD-like shift in mobility as a result of phosphorylation-like changes, we conclude that they have the characteristics of hyperphosphorylated tau. These mutants will therefore be referred to as pseudo-hyperphosphorylated tau throughout the manuscript. On the basis of the observations that pseudohyperphosphorylated tau has decreased affinity for microtubules and reduced inducer-initiated rates of nucleation and polymerization, we propose that this combination could be the cause of the increased cytotoxicity of hyperphosphorylated tau in Alzheimer's disease and also explain the potentially beneficial role of tau polymerization and NFT formation. PubMed:19459590

This result is supported by recent studies showing that the interaction between Fyn and tau is regulated through tau phosphorylation at the AT8 site, increasing tau-Fyn interaction by 42-fold after tau is phosphorylated or bearing a phosphomimetic mutation at the AT8 site (63). In our experiments, tau phosphorylation at AT8 is strongly up-regulated through the activation of NMDA receptors (Fig. 3), suggesting that NMDA receptor activation could massively enhance the interaction between tau and Fyn. PubMed:22833681

Phosphorylation at the epitope Ser202/Thr205 is regarded as a good marker for late-stage NFTs (5, 72). Hyman and colleagues (5) demonstrated that AT8 immunoreactivity is present primarily in eNFTs and in certain cases in iNFTs. These investigators also found that AT8 revealed dense neuropil thread staining. PubMed:22253473

Thus, the increase in ac-tau induced by SIRT1 deficiency is accompanied by accumulation of pathogenic p-tau in primary neurons. In mouse brains, deleting SIRT1, which elevated ac-tau, also increased AT8-positive p-tau. PubMed:20869593

Thus, the increase in ac-tau induced by SIRT1 deficiency is accompanied by accumulation of pathogenic p-tau in primary neurons. In mouse brains, deleting SIRT1, which elevated ac-tau, also increased AT8-positive p-tau. PubMed:20869593

QA appears to act through NMDA receptor activation similar to other agonists, glutamate and NMDA and was abrogated by the NMDAR antagonist memantine. NMDA receptor agonists, glutamate and NMDA at equimolar concentrations (500 nM) increased tau phosphorylation at serine 199/202 (AT8) and threonine 231 (AT-180), similar to QA. PubMed:19623258