a(HBP:"Tau oligomers")
For example, as discussed above, certain modified forms of tau, such as caspase-cleaved tau, have a stronger tendency to aggregate. As tau begins to assemble into oligomers, it may become increasingly undesirable as a proteasomal substrate. These low-order, soluble oligomers may be preferentially degraded by autophagy. PubMed:24027553
For example, as discussed above, certain modified forms of tau, such as caspase-cleaved tau, have a stronger tendency to aggregate. As tau begins to assemble into oligomers, it may become increasingly undesirable as a proteasomal substrate. These low-order, soluble oligomers may be preferentially degraded by autophagy. PubMed:24027553
Indeed, early pre-tangle neurons within the hippocampus were labeled with all antibodies in Braak I-II cases (Fig. 5A–D) PubMed:27574109
Similarly, the characteristic Pick bodies in the frontal cortex were well labeled by TNT1, TOC1 and R1 in PiD tissue (Fig. 5M–P) PubMed:27574109
Indeed, early pre-tangle neurons within the hippocampus were labeled with all antibodies in Braak I-II cases (Fig. 5A–D) PubMed:27574109
In CBD, the characteristic astrocytic pathology (e.g. astrocytic plaques) showed extensive co-localization between TNT1, TOC1 and R1 in the frontal cortex (Fig. 5I–L). PubMed:27574109
Similarly, the soluble fraction from AD contained the greatest level of TOC1 reactivity, followed by CBD and then PiD had the lowest signal (Fig. 6D; one-way ANOVA with Holm-Sidak post-hoc, F(2,9) = 16.57, p = 0.001) PubMed:27574109
TOC1 detected significantly more oligomeric tau in AD compared to CBD and PiD and more in CBD compared to PiD (Fig. 6G; one-way ANOVA with Holm-Sidak post-hoc, F(2,9) = 35.32, p < 0.0001) PubMed:27574109
As expected, monomer and aggregated samples of all six tau isoforms showed equal reactivity for TNT1 and TOC1 when the samples were denatured because this exposes the epitopes making them equally accessible (Student’s t-tests, for all comparisons p > 0.05; Fig. 3C–H) PubMed:27574109
Comparisons between isoform monomers showed that hT39 monomer signal was significantly higher than hT24 and hT23 monomers (Kruskal-Wallis ANOVA with Dunn’s post-hoc, H = 18.6, p = 0.0023) PubMed:27574109
As expected, monomer and aggregated samples of all six tau isoforms showed equal reactivity for TNT1 and TOC1 when the samples were denatured because this exposes the epitopes making them equally accessible (Student’s t-tests, for all comparisons p > 0.05; Fig. 3C–H) PubMed:27574109
Comparisons between isoform monomers showed that hT39 monomer signal was significantly higher than hT24 and hT23 monomers (Kruskal-Wallis ANOVA with Dunn’s post-hoc, H = 18.6, p = 0.0023) PubMed:27574109
As expected, monomer and aggregated samples of all six tau isoforms showed equal reactivity for TNT1 and TOC1 when the samples were denatured because this exposes the epitopes making them equally accessible (Student’s t-tests, for all comparisons p > 0.05; Fig. 3C–H) PubMed:27574109
As expected, monomer and aggregated samples of all six tau isoforms showed equal reactivity for TNT1 and TOC1 when the samples were denatured because this exposes the epitopes making them equally accessible (Student’s t-tests, for all comparisons p > 0.05; Fig. 3C–H) PubMed:27574109
As expected, monomer and aggregated samples of all six tau isoforms showed equal reactivity for TNT1 and TOC1 when the samples were denatured because this exposes the epitopes making them equally accessible (Student’s t-tests, for all comparisons p > 0.05; Fig. 3C–H) PubMed:27574109
Comparisons between isoform monomers showed that hT39 monomer signal was significantly higher than hT24 and hT23 monomers (Kruskal-Wallis ANOVA with Dunn’s post-hoc, H = 18.6, p = 0.0023) PubMed:27574109
As expected, monomer and aggregated samples of all six tau isoforms showed equal reactivity for TNT1 and TOC1 when the samples were denatured because this exposes the epitopes making them equally accessible (Student’s t-tests, for all comparisons p > 0.05; Fig. 3C–H) PubMed:27574109
Indeed, early pre-tangle neurons within the hippocampus were labeled with all antibodies in Braak I-II cases (Fig. 5A–D) PubMed:27574109
In severe AD cases (i.e. Braak stage V-VI), all markers continue to colocalize in classic NFTs within the hippocampus that characterize AD tau pathology (Fig. 5E–H) PubMed:27574109
The hT24 aggregates showed the highest TOC1 signal, which reached significance compared to hT40, hT39, hT37 and hT23 aggregates, while hT34 aggregates were significantly different from hT39, hT37 and hT23 aggregates, and both hT40 and hT39 aggregates are significantly higher than hT37 and hT23 (one-way ANOVA with Holm-Sidak post-hoc, F(5, 18) = 50.77, p < 0.0001) PubMed:27574109
Aggregated samples for all six isoforms showed significant increases in TOC1 reactivity when compared to their respective monomer samples (Fig. 3B; Mann-Whitney tests, for all comparisons p = 0.029) PubMed:27574109
As expected, monomer and aggregated samples of all six tau isoforms showed equal reactivity for TNT1 and TOC1 when the samples were denatured because this exposes the epitopes making them equally accessible (Student’s t-tests, for all comparisons p > 0.05; Fig. 3C–H) PubMed:27574109
The hT24 aggregates showed the highest TOC1 signal, which reached significance compared to hT40, hT39, hT37 and hT23 aggregates, while hT34 aggregates were significantly different from hT39, hT37 and hT23 aggregates, and both hT40 and hT39 aggregates are significantly higher than hT37 and hT23 (one-way ANOVA with Holm-Sidak post-hoc, F(5, 18) = 50.77, p < 0.0001) PubMed:27574109
Aggregated samples for all six isoforms showed significant increases in TOC1 reactivity when compared to their respective monomer samples (Fig. 3B; Mann-Whitney tests, for all comparisons p = 0.029) PubMed:27574109
As expected, monomer and aggregated samples of all six tau isoforms showed equal reactivity for TNT1 and TOC1 when the samples were denatured because this exposes the epitopes making them equally accessible (Student’s t-tests, for all comparisons p > 0.05; Fig. 3C–H) PubMed:27574109
The hT24 aggregates showed the highest TOC1 signal, which reached significance compared to hT40, hT39, hT37 and hT23 aggregates, while hT34 aggregates were significantly different from hT39, hT37 and hT23 aggregates, and both hT40 and hT39 aggregates are significantly higher than hT37 and hT23 (one-way ANOVA with Holm-Sidak post-hoc, F(5, 18) = 50.77, p < 0.0001) PubMed:27574109
Aggregated samples for all six isoforms showed significant increases in TOC1 reactivity when compared to their respective monomer samples (Fig. 3B; Mann-Whitney tests, for all comparisons p = 0.029) PubMed:27574109
As expected, monomer and aggregated samples of all six tau isoforms showed equal reactivity for TNT1 and TOC1 when the samples were denatured because this exposes the epitopes making them equally accessible (Student’s t-tests, for all comparisons p > 0.05; Fig. 3C–H) PubMed:27574109
The hT24 aggregates showed the highest TOC1 signal, which reached significance compared to hT40, hT39, hT37 and hT23 aggregates, while hT34 aggregates were significantly different from hT39, hT37 and hT23 aggregates, and both hT40 and hT39 aggregates are significantly higher than hT37 and hT23 (one-way ANOVA with Holm-Sidak post-hoc, F(5, 18) = 50.77, p < 0.0001) PubMed:27574109
Aggregated samples for all six isoforms showed significant increases in TOC1 reactivity when compared to their respective monomer samples (Fig. 3B; Mann-Whitney tests, for all comparisons p = 0.029) PubMed:27574109
As expected, monomer and aggregated samples of all six tau isoforms showed equal reactivity for TNT1 and TOC1 when the samples were denatured because this exposes the epitopes making them equally accessible (Student’s t-tests, for all comparisons p > 0.05; Fig. 3C–H) PubMed:27574109
The hT24 aggregates showed the highest TOC1 signal, which reached significance compared to hT40, hT39, hT37 and hT23 aggregates, while hT34 aggregates were significantly different from hT39, hT37 and hT23 aggregates, and both hT40 and hT39 aggregates are significantly higher than hT37 and hT23 (one-way ANOVA with Holm-Sidak post-hoc, F(5, 18) = 50.77, p < 0.0001) PubMed:27574109
Aggregated samples for all six isoforms showed significant increases in TOC1 reactivity when compared to their respective monomer samples (Fig. 3B; Mann-Whitney tests, for all comparisons p = 0.029) PubMed:27574109
As expected, monomer and aggregated samples of all six tau isoforms showed equal reactivity for TNT1 and TOC1 when the samples were denatured because this exposes the epitopes making them equally accessible (Student’s t-tests, for all comparisons p > 0.05; Fig. 3C–H) PubMed:27574109
The hT24 aggregates showed the highest TOC1 signal, which reached significance compared to hT40, hT39, hT37 and hT23 aggregates, while hT34 aggregates were significantly different from hT39, hT37 and hT23 aggregates, and both hT40 and hT39 aggregates are significantly higher than hT37 and hT23 (one-way ANOVA with Holm-Sidak post-hoc, F(5, 18) = 50.77, p < 0.0001) PubMed:27574109
Aggregated samples for all six isoforms showed significant increases in TOC1 reactivity when compared to their respective monomer samples (Fig. 3B; Mann-Whitney tests, for all comparisons p = 0.029) PubMed:27574109
As expected, monomer and aggregated samples of all six tau isoforms showed equal reactivity for TNT1 and TOC1 when the samples were denatured because this exposes the epitopes making them equally accessible (Student’s t-tests, for all comparisons p > 0.05; Fig. 3C–H) PubMed:27574109
Similarly, the soluble fraction from AD contained the greatest level of TOC1 reactivity, followed by CBD and then PiD had the lowest signal (Fig. 6D; one-way ANOVA with Holm-Sidak post-hoc, F(2,9) = 16.57, p = 0.001) PubMed:27574109
TOC1 detected significantly more oligomeric tau in AD compared to CBD and PiD and more in CBD compared to PiD (Fig. 6G; one-way ANOVA with Holm-Sidak post-hoc, F(2,9) = 35.32, p < 0.0001) PubMed:27574109
Similarly, the soluble fraction from AD contained the greatest level of TOC1 reactivity, followed by CBD and then PiD had the lowest signal (Fig. 6D; one-way ANOVA with Holm-Sidak post-hoc, F(2,9) = 16.57, p = 0.001) PubMed:27574109
TOC1 detected significantly more oligomeric tau in AD compared to CBD and PiD and more in CBD compared to PiD (Fig. 6G; one-way ANOVA with Holm-Sidak post-hoc, F(2,9) = 35.32, p < 0.0001) PubMed:27574109
In general, the remarkable co-localization between TNT1, TOC1 and R1 in all tauopathies confirms that PAD exposure and tau oligomerization occur simultaneously in cells displaying tau pathology, irrespective of isoform composition PubMed:27574109
Additionally, a significant reduction (P<0.05) in tau oligomers levels (TOC1 immunopositive) was detected both in the brain and the spinal cord of Tg Tau P301S treated with anatabine using dot-blots (Figure 8). DOI:10.4172/2168-975X.1000126
We observed that anatabine significantly prevented the formation of MC1-positive tau oligomers (Figure 9) by western-blots in both the brain and the spinal cord of Tg Tau P301S mice (T-tests, P<0.05) further confirming the data obtained with the dot-blots DOI:10.4172/2168-975X.1000126
Monomeric, oligomeric and sonicated fibrils were efficiently internalized, while fibril samples were not (Fig. 1c and Supplementary Fig. 1d) PubMed:29686391
Monomeric, oligomeric and sonicated fibrils were efficiently internalized, while fibril samples were not (Fig. 1c and Supplementary Fig. 1d) PubMed:29686391
Tau protein can form multiple quaternary structures in solution, and recent evidence suggests that small tau oligomeric species may play a critical role in the spread of tau pathology and neurotoxicity PubMed:29686391
These single gene knockdowns repressed uptake of tau monomer by over 50% (Fig. 2b) and also reduced the uptake of tau oligomers (Fig. 2c) PubMed:29686391
These single gene knockdowns repressed uptake of tau monomer by over 50% (Fig. 2b) and also reduced the uptake of tau oligomers (Fig. 2c) PubMed:29686391
These single gene knockdowns repressed uptake of tau monomer by over 50% (Fig. 2b) and also reduced the uptake of tau oligomers (Fig. 2c) PubMed:29686391
Tau protein can form multiple quaternary structures in solution, and recent evidence suggests that small tau oligomeric species may play a critical role in the spread of tau pathology and neurotoxicity PubMed:29686391
Hyper-phosphorylated tau assembles into small aggregates known as tau oligomers in route of NFT formation PubMed:28420982
As hyperphosphorylated tau dislodges from microtubules, its affinity for other tau monomers leads individual tau to bind each other, forming oligomeric tau, a detergent-soluble aggregate PubMed:28420982
Recently, data has shown that injected tau oligomers colocalize with the mitochondrial marker porin, suggesting a pathological relationship PubMed:28420982
The onset of clinical symptoms in AD and PSP brains correlate with elevated levels of tau oligomer (Maeda et al., 2006, 2007; Patterson et al., 2011; Lasagna-Reeves et al., 2012b; Gerson et al., 2014a) PubMed:28420982
The onset of clinical symptoms in AD and PSP brains correlate with elevated levels of tau oligomer (Maeda et al., 2006, 2007; Patterson et al., 2011; Lasagna-Reeves et al., 2012b; Gerson et al., 2014a) PubMed:28420982
In the same study, we found that high levels of Aha1 in a tau transgenic mouse model increased tau oligomers as well as neuronal loss concomitant with cognitive deficits (Shelton et al., 2017). PubMed:29311797
Employing recombinant full-length hT40, we observe the presence of oligomers approximately 15 min after the addition of the anionic inducer arachidonic acid, whereas filament formation requires 5–6 h to attain steady state (Figures 1A–1C) PubMed:22817713
Compared to monomers, aggregation significantly increased PAD exposure for both hT40 and S422E samples (Fig. 3B; F(1,12) = 685.8, p b 0.0001), as indicated by increased TNT1 reactivity. Aggregation also significantly increased oligomer formation (TOC1 reactivity) compared to monomers in both hT40 and S422E samples (Fig. 3C; F(1,12) = 109.3, p b 0.0001). PubMed:27373205
For both tau constructs, there were significantly more oligomer-type aggregates than short or long filaments formed, but no significant difference between the numbers of short or long filament (Fig. 2E; F(2,12) = 86.64, p b 0.0001). S422E did not differ significantly from hT40 in the number of oligomers, short filaments, or long filaments formed (F(1,12) = 0.05, p = 0.83). PubMed:27373205
Compared to monomers, aggregation significantly increased PAD exposure for both hT40 and S422E samples (Fig. 3B; F(1,12) = 685.8, p b 0.0001), as indicated by increased TNT1 reactivity. Aggregation also significantly increased oligomer formation (TOC1 reactivity) compared to monomers in both hT40 and S422E samples (Fig. 3C; F(1,12) = 109.3, p b 0.0001). PubMed:27373205
For both tau constructs, there were significantly more oligomer-type aggregates than short or long filaments formed, but no significant difference between the numbers of short or long filament (Fig. 2E; F(2,12) = 86.64, p b 0.0001). S422E did not differ significantly from hT40 in the number of oligomers, short filaments, or long filaments formed (F(1,12) = 0.05, p = 0.83). PubMed:27373205
Time-course aggregation analysis revealed that dimerization precedes tau oligomerization which, in turn, is an earlier event than the formation of full-length filaments PubMed:22817713
TNT1 also co-localizes in tissue with the phospho-epitope defined by the AT8 antibody, indicating that PAD exposure represents an early event in AD pathology PubMed:22817713
TOC1’s immunoreactivity is greatly elevated in AD brains compared with healthy controls, but co-localizes best with early-stage markers for AD pathogenesis such as pS422 [16] PubMed:22817713
TNT1 also co-localizes in tissue with the phospho-epitope defined by the AT8 antibody, indicating that PAD exposure represents an early event in AD pathology PubMed:22817713
TOC1’s immunoreactivity is greatly elevated in AD brains compared with healthy controls, but co-localizes best with early-stage markers for AD pathogenesis such as pS422 [16] PubMed:22817713
Tau contains cysteine residues in the microtubule binding region following alternative splicing of exon 10, and formation of intermolecular cysteine disulfide bonds accelerates tau aggregation. 8-Nitro-cGMP (novel second messenger of NO) exposure induced S-guanylation of tau both in vitro and in tau-overexpressed HEK293T cells. S-guanylated tau inhibited heparin-induced tau aggregation (thioflavin T). S-guanylated tau could not form tau granules and fibrils (AFM) inhibited at the step of tau oligomer formation. In P301L tau-expressing Neuro2A cells, 8-nitro-cGMP reduced the amount of sarcosyl-insoluble tau. NO-linked chemical modification on cysteine residues of tau could block tau aggregation PubMed:27601475
Tau Oligomers co-localize with astrocytes, microglia, and HMGB1, a pro-inflammatory cytokine, are present in the retina and are associated with inflammatory cells. PubMed:27716675
Several lines of evidence in other tauopathies suggest that tau oligomer formation induces neurotoxicity and that tau oligomer-mediated neurotoxicity involves induction of axonal dysfunction through exposure of an N-terminal motif in tau, the phosphatase-activating domain (PAD). PubMed:26671985
This revealed a significant increase of oligomeric Tau forms in AAV– Otub1-infected neurons compared with AAV–GFP-infected neurons (Fig. 4c). PubMed:28083634
The induction of oligomeric Tau forms was further confirmed using dot-blot analysis with T22 antibody (Fig. 4d), revealing a significant increase in oligomeric Tau following expression of Otub1. PubMed:28083634
This revealed a significant increase of monomeric Tau and oligomeric Tau in AAV– Otub1-injected mice compared with AAV–GFP-injected mice (Fig. 7c). PubMed:28083634
This revealed significantly increased oligomeric Tau in AAV– Otub1-injected mice compared with AAV–GFP-injected control cases (Fig. 7d). PubMed:28083634
This revealed significantly increased oligomeric Tau forms, following expression of wild-type Otub1, but not following expression of GFP or of the catalytically inactive form of Otub1 (C91A) (Fig. 8c). PubMed:28083634
This revealed significantly increased oligomeric Tau forms, following expression of wild-type Otub1, but not following expression of GFP or of the catalytically inactive form of Otub1 (C91A) (Fig. 8c). PubMed:28083634
Analysis of sarkosyl extracts of brain homogenates of mice expressing the pro-aggregant repeat domain TauRDΔK revealed that oligomers are present, partly in a disulfide–cross-linked form (Supplementary Fig. 1). PubMed:28528849
Whereas control brain homogenate exhibited mainly Tau monomer, the AD brain contained a range of Tau assemblies ranging from n = 1 to n > 20 (Fig. 7, A and B). PubMed:25887395
In addition, this A152T tau enhances the formation of oligomers but not fibres PubMed:26631930
In an analogy to the evolution of concepts in the ‘amyloid cascade hypothesis’, which proposes that soluble oligomers — rather than insoluble aggregates of amyloid peptides — are the causative agents of neurodegeneration in AD, recent studies have suggested tau oligomers to be the toxic species, and indeed levels of SDS-stable tau oligomers are increased in AD and PSP brains. PubMed:26631930
In an analogy to the evolution of concepts in the ‘amyloid cascade hypothesis’, which proposes that soluble oligomers — rather than insoluble aggregates of amyloid peptides — are the causative agents of neurodegeneration in AD, recent studies have suggested tau oligomers to be the toxic species, and indeed levels of SDS-stable tau oligomers are increased in AD and PSP brains. PubMed:26631930
Indeed, early pre-tangle neurons within the hippocampus were labeled with all antibodies in Braak I-II cases (Fig. 5A–D) PubMed:27574109
Indeed, early pre-tangle neurons within the hippocampus were labeled with all antibodies in Braak I-II cases (Fig. 5A–D) PubMed:27574109
Indeed, early pre-tangle neurons within the hippocampus were labeled with all antibodies in Braak I-II cases (Fig. 5A–D) PubMed:27574109
In severe AD cases (i.e. Braak stage V-VI), all markers continue to colocalize in classic NFTs within the hippocampus that characterize AD tau pathology (Fig. 5E–H) PubMed:27574109
In CBD, the characteristic astrocytic pathology (e.g. astrocytic plaques) showed extensive co-localization between TNT1, TOC1 and R1 in the frontal cortex (Fig. 5I–L). PubMed:27574109
Similarly, the soluble fraction from AD contained the greatest level of TOC1 reactivity, followed by CBD and then PiD had the lowest signal (Fig. 6D; one-way ANOVA with Holm-Sidak post-hoc, F(2,9) = 16.57, p = 0.001) PubMed:27574109
TOC1 detected significantly more oligomeric tau in AD compared to CBD and PiD and more in CBD compared to PiD (Fig. 6G; one-way ANOVA with Holm-Sidak post-hoc, F(2,9) = 35.32, p < 0.0001) PubMed:27574109
Similarly, the characteristic Pick bodies in the frontal cortex were well labeled by TNT1, TOC1 and R1 in PiD tissue (Fig. 5M–P) PubMed:27574109
In general, the remarkable co-localization between TNT1, TOC1 and R1 in all tauopathies confirms that PAD exposure and tau oligomerization occur simultaneously in cells displaying tau pathology, irrespective of isoform composition PubMed:27574109
Similarly, the soluble fraction from AD contained the greatest level of TOC1 reactivity, followed by CBD and then PiD had the lowest signal (Fig. 6D; one-way ANOVA with Holm-Sidak post-hoc, F(2,9) = 16.57, p = 0.001) PubMed:27574109
TOC1 detected significantly more oligomeric tau in AD compared to CBD and PiD and more in CBD compared to PiD (Fig. 6G; one-way ANOVA with Holm-Sidak post-hoc, F(2,9) = 35.32, p < 0.0001) PubMed:27574109
Similarly, the soluble fraction from AD contained the greatest level of TOC1 reactivity, followed by CBD and then PiD had the lowest signal (Fig. 6D; one-way ANOVA with Holm-Sidak post-hoc, F(2,9) = 16.57, p = 0.001) PubMed:27574109
TOC1 detected significantly more oligomeric tau in AD compared to CBD and PiD and more in CBD compared to PiD (Fig. 6G; one-way ANOVA with Holm-Sidak post-hoc, F(2,9) = 35.32, p < 0.0001) PubMed:27574109
Tau protein can form multiple quaternary structures in solution, and recent evidence suggests that small tau oligomeric species may play a critical role in the spread of tau pathology and neurotoxicity PubMed:29686391
Tau protein can form multiple quaternary structures in solution, and recent evidence suggests that small tau oligomeric species may play a critical role in the spread of tau pathology and neurotoxicity PubMed:29686391
Monomeric, oligomeric and sonicated fibrils were efficiently internalized, while fibril samples were not (Fig. 1c and Supplementary Fig. 1d) PubMed:29686391
Monomeric, oligomeric and sonicated fibrils were efficiently internalized, while fibril samples were not (Fig. 1c and Supplementary Fig. 1d) PubMed:29686391
While evidence indicates that these deposits are not toxic, many studies suggest that the tau oligomer, an intermediate entity, is likely responsible for disease onset PubMed:28420982
These tau oligomers potentiate neuronal damage, leading to neurodegeneration and traumatic brain injury (Hawkins et al., 2013; Gerson et al., 2014a, 2016; Sengupta et al., 2015). Moreover, they have been implicated in synaptic loss as shown in studies of wild-type human tau transgenic mice (Spires et al., 2006; Berger et al., 2007; Clavaguera et al., 2013) PubMed:28420982
These studies demonstrate that tau oligomers may be the toxic entities responsible for neurodegeneration in tauopathies (Ward et al., 2012 PubMed:28420982
These tau oligomers potentiate neuronal damage, leading to neurodegeneration and traumatic brain injury (Hawkins et al., 2013; Gerson et al., 2014a, 2016; Sengupta et al., 2015). Moreover, they have been implicated in synaptic loss as shown in studies of wild-type human tau transgenic mice (Spires et al., 2006; Berger et al., 2007; Clavaguera et al., 2013) PubMed:28420982
These tau oligomers potentiate neuronal damage, leading to neurodegeneration and traumatic brain injury (Hawkins et al., 2013; Gerson et al., 2014a, 2016; Sengupta et al., 2015). Moreover, they have been implicated in synaptic loss as shown in studies of wild-type human tau transgenic mice (Spires et al., 2006; Berger et al., 2007; Clavaguera et al., 2013) PubMed:28420982
When the oligomer lengthens, it adapts a beta-sheet structure and transforms into a detergent-insoluble aggregate with granular appearance under Atomic Force Microscopy (AFM) PubMed:28420982
The onset of clinical symptoms in AD and PSP brains correlate with elevated levels of tau oligomer (Maeda et al., 2006, 2007; Patterson et al., 2011; Lasagna-Reeves et al., 2012b; Gerson et al., 2014a) PubMed:28420982
The onset of clinical symptoms in AD and PSP brains correlate with elevated levels of tau oligomer (Maeda et al., 2006, 2007; Patterson et al., 2011; Lasagna-Reeves et al., 2012b; Gerson et al., 2014a) PubMed:28420982
When tau oligomers, rather than tau monomers or fibrils, are injected into the brain of wild-type mice, cognitive, synaptic, and mitochondrial abnormalities follow (Lasagna- Reeves et al., 2011; Castillo-Carranza et al., 2014b) PubMed:28420982
When tau oligomers, rather than tau monomers or fibrils, are injected into the brain of wild-type mice, cognitive, synaptic, and mitochondrial abnormalities follow (Lasagna- Reeves et al., 2011; Castillo-Carranza et al., 2014b) PubMed:28420982
When tau oligomers, rather than tau monomers or fibrils, are injected into the brain of wild-type mice, cognitive, synaptic, and mitochondrial abnormalities follow (Lasagna- Reeves et al., 2011; Castillo-Carranza et al., 2014b) PubMed:28420982
This indicates that tauopathies progress via a prion-like mechanism dependent upon tau oligomers (Gerson and Kayed, 2013; Castillo-Carranza et al., 2014b) PubMed:28420982
These studies demonstrate that tau oligomers may be the toxic entities responsible for neurodegeneration in tauopathies (Ward et al., 2012 PubMed:28420982
With this concept, tau may be able to translocate between neurons and augment toxic tau components; in fact, evidence suggests probability of tau oligomer propagation between synaptically connected neurons (Gendreau and Hall, 2013; Pooler et al., 2013b) PubMed:28420982
Further, mice injected with tau oligomers in the proximity of the hippocampus experienced immediate memory impairment (Lasagna-Reeves et al., 2011) PubMed:28420982
The study discovered that APFs form after tau oligomer formation and bypass higher NFT aggregate formation PubMed:28420982
Oligomeric tau intermediates decrease cell viability (Flach et al., 2012) PubMed:28420982
Recently, data has shown that injected tau oligomers colocalize with the mitochondrial marker porin, suggesting a pathological relationship PubMed:28420982
In fact, tau oligomers might disrupt microtubule stability and trafficking, thus affecting organelle distribution PubMed:28420982
Also, data shows low levels of complex I in brain hemispheres injected with tau oligomers when compared to brains injected with monomers or fibrils PubMed:28420982
These results imply that tau oligomers initially affect complex I activity and may directly or indirectly disturb the later stage of complex V ATP synthesis (Lasagna-Reeves et al., 2011) PubMed:28420982
These results imply that tau oligomers initially affect complex I activity and may directly or indirectly disturb the later stage of complex V ATP synthesis (Lasagna-Reeves et al., 2011) PubMed:28420982
Hemispheres injected with tau oligomers were found to have increased levels of caspase-9 activation (Lasagna-Reeves et al., 2011) PubMed:28420982
Suggestively, as tau oligomers concentrate at the mitochondrial membrane, cytochrome C is released, leading to caspase-9 activation via a complex with apoptotic-peptidase activating- factor-1 (Apaf-1; Li et al., 1997) PubMed:28420982
Together, these findings support the hypothesis that tau oligomers are the toxic form of tau in neurodegenerative disease PubMed:22817713
This indicates that tau oligomers represent the main toxic species responsible for neurodegeneration associated with AD PubMed:22817713
Time-course aggregation analysis revealed that dimerization precedes tau oligomerization which, in turn, is an earlier event than the formation of full-length filaments PubMed:22817713
TOC1’s immunoreactivity is greatly elevated in AD brains compared with healthy controls, but co-localizes best with early-stage markers for AD pathogenesis such as pS422 [16] PubMed:22817713
TNT1 also co-localizes in tissue with the phospho-epitope defined by the AT8 antibody, indicating that PAD exposure represents an early event in AD pathology PubMed:22817713
TNT1 also co-localizes in tissue with the phospho-epitope defined by the AT8 antibody, indicating that PAD exposure represents an early event in AD pathology PubMed:22817713
This indicates that tau oligomers represent the main toxic species responsible for neurodegeneration associated with AD PubMed:22817713
Tau Oligomers co-localize with astrocytes, microglia, and HMGB1, a pro-inflammatory cytokine, are present in the retina and are associated with inflammatory cells. PubMed:27716675
This work supports the hypothesis that tau oligomers are toxic species that can drive the spread of tau pathology and neurodegeneration. PubMed:27716675
Several lines of evidence in other tauopathies suggest that tau oligomer formation induces neurotoxicity and that tau oligomer-mediated neurotoxicity involves induction of axonal dysfunction through exposure of an N-terminal motif in tau, the phosphatase-activating domain (PAD). PubMed:26671985
Several lines of evidence in other tauopathies suggest that tau oligomer formation induces neurotoxicity and that tau oligomer-mediated neurotoxicity involves induction of axonal dysfunction through exposure of an N-terminal motif in tau, the phosphatase-activating domain (PAD). PubMed:26671985
Several lines of evidence in other tauopathies suggest that tau oligomer formation induces neurotoxicity and that tau oligomer-mediated neurotoxicity involves induction of axonal dysfunction through exposure of an N-terminal motif in tau, the phosphatase-activating domain (PAD). PubMed:26671985
Recently, extracellular tau oligomers were shown to impair long term potentiation (LTP) and memory [40]. PubMed:28528849
Recently, extracellular tau oligomers were shown to impair long term potentiation (LTP) and memory [40]. PubMed:28528849
Whereas control brain homogenate exhibited mainly Tau monomer, the AD brain contained a range of Tau assemblies ranging from n = 1 to n > 20 (Fig. 7, A and B). PubMed:25887395
Indeed, evidence from both human and mouse studies indicates that soluble oligomers rather than insoluble aggregates are toxic to normal neurons (70). PubMed:29191965
In an analogy to the evolution of concepts in the ‘amyloid cascade hypothesis’, which proposes that soluble oligomers — rather than insoluble aggregates of amyloid peptides — are the causative agents of neurodegeneration in AD, recent studies have suggested tau oligomers to be the toxic species, and indeed levels of SDS-stable tau oligomers are increased in AD and PSP brains. PubMed:26631930
In an analogy to the evolution of concepts in the ‘amyloid cascade hypothesis’, which proposes that soluble oligomers — rather than insoluble aggregates of amyloid peptides — are the causative agents of neurodegeneration in AD, recent studies have suggested tau oligomers to be the toxic species, and indeed levels of SDS-stable tau oligomers are increased in AD and PSP brains. PubMed:26631930
In an analogy to the evolution of concepts in the ‘amyloid cascade hypothesis’, which proposes that soluble oligomers — rather than insoluble aggregates of amyloid peptides — are the causative agents of neurodegeneration in AD, recent studies have suggested tau oligomers to be the toxic species, and indeed levels of SDS-stable tau oligomers are increased in AD and PSP brains. PubMed:26631930
Some studies showed in cell toxicity assays that tau oligomers made from pro-aggregant recombinant tau were toxic to cultured cells; other studies in cultured neurons found that oligomers induced only local neurotoxicity that led to loss of spines PubMed:26631930
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