Log in

Relevant bibliographies by topics / Tau seeding / Journal articles

Journal articles on the topic 'Tau seeding'

To see the other types of publications on this topic, follow the link: Tau seeding.

Author: Grafiati

Published: 10 December 2022

Last updated: 29 January 2023

Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles

Select a source type:

Consult the top 50 journal articles for your research on the topic 'Tau seeding.'

Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.

You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.

Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.

1

Andrés-Benito, Pol, Margarita Carmona, Mónica Jordán, Joaquín Fernández-Irigoyen, Enrique Santamaría, José Antoni del Rio, and Isidro Ferrer. "Host Tau Genotype Specifically Designs and Regulates Tau Seeding and Spreading and Host Tau Transformation Following Intrahippocampal Injection of Identical Tau AD Inoculum." International Journal of Molecular Sciences 23, no. 2 (January 10, 2022): 718. http://dx.doi.org/10.3390/ijms23020718.

Full text

Abstract:

Several studies have demonstrated the different characteristics of tau seeding and spreading following intracerebral inoculation in murine models of tau-enriched fractions of brain homogenates from AD and other tauopathies. The present study is centered on the importance of host tau in tau seeding and the molecular changes associated with the transformation of host tau into abnormal tau. The brains of three adult murine genotypes expressing different forms of tau—WT (murine 4Rtau), hTau (homozygous transgenic mice knock-out for murine tau protein and heterozygous expressing human forms of 3Rtau and 4Rtau proteins), and mtWT (homozygous transgenic mice knock-out for murine tau protein)—were analyzed following unilateral hippocampal inoculation of sarkosyl-insoluble tau fractions from the same AD and control cases. The present study reveals that (a) host tau is mandatory for tau seeding and spreading following tau inoculation from sarkosyl-insoluble fractions obtained from AD brains; (b) tau seeding does not occur following intracerebral inoculation of sarkosyl-insoluble fractions from controls; (c) tau seeding and spreading are characterized by variable genotype-dependent tau phosphorylation and tau nitration, MAP2 phosphorylation, and variable activation of kinases that co-localize with abnormal tau deposits; (d) transformation of host tau into abnormal tau is an active process associated with the activation of specific kinases; (e) tau seeding is accompanied by modifications in tau splicing, resulting in the expression of new 3Rtau and 4Rtau isoforms, thus indicating that inoculated tau seeds have the capacity to model exon 10 splicing of the host mapt or MAPT with a genotype-dependent pattern; (e) selective regional and cellular vulnerabilities, and different molecular compositions of the deposits, are dependent on the host tau of mice injected with identical AD tau inocula.

APA, Harvard, Vancouver, ISO, and other styles

2

Wu, Ruozhen, Jianlan Gu, Dingwei Zhou, Yunn Chyn Tung, Nana Jin, Dandan Chu, Wen Hu, et al. "Seeding-Competent Tau in Gray Matter Versus White Matter of Alzheimer’s Disease Brain." Journal of Alzheimer's Disease 79, no. 4 (February 16, 2021): 1647–59. http://dx.doi.org/10.3233/jad-201290.

Full text

Abstract:

Background: Neurofibrillary pathology of abnormally hyperphosphorylated tau spreads along neuroanatomical connections, underlying the progression of Alzheimer’s disease (AD). The propagation of tau pathology to axonally connected brain regions inevitably involves trafficking of seeding-competent tau within the axonal compartment of the neuron. Objective: To determine the seeding activity of tau in cerebral gray and white matters of AD. Methods: Levels of total tau, hyperphosphorylation of tau, and SDS- and β-mercaptoethanol–resistant high molecular weight tau (HMW-tau) in crude extracts from gray and white matters of AD frontal lobes were analyzed by immuno-blots. Tau seeding activity was quantitatively assessed by measuring RIPA buffer–insoluble tau in HEK-293FT/tau151-391 cells treated with brain extracts. Results: We found a comparable level of soluble tau in gray matter versus white matter of control brains, but a higher level of soluble tau in gray matter than white matter of AD brains. In AD brains, tau is hyperphosphorylated in both gray and white matters, with a higher level in the former. The extracts of both gray and white matters of AD brains seeded tau aggregation in HEK-293FT/tau151–391 cells but the white matter showed less potency. Seeding activity of tau in brain extracts was positively correlated with the levels of tau hyperphosphorylation and HMW-tau. RIPA-insoluble tau, but not RIPA-soluble tau, was hyperphosphorylated tau at multiple sites. Conclusion: Both gray and white matters of AD brain contain seeding-competent tau that can template aggregation of hyperphosphorylated tau, but the seeding potency is markedly higher in gray matter than in white matter.

APA, Harvard, Vancouver, ISO, and other styles

3

Ferrer, Isidro, Maria Victoria Zelaya, Meritxell Aguiló García, Margarita Carmona, Irene López‐González, Pol Andrés‐Benito, Laia Lidón, Rosalina Gavín, Paula Garcia‐Esparcia, and José Antonio Rio. "Relevance of host tau in tau seeding and spreading in tauopathies." Brain Pathology 30, no. 2 (August 27, 2019): 298–318. http://dx.doi.org/10.1111/bpa.12778.

Full text

APA, Harvard, Vancouver, ISO, and other styles

4

Holmes, B. B., J. L. Furman, T. E. Mahan, T. R. Yamasaki, H. Mirbaha, W. C. Eades, L. Belaygorod, N. J. Cairns, D. M. Holtzman, and M. I. Diamond. "Proteopathic tau seeding predicts tauopathy in vivo." Proceedings of the National Academy of Sciences 111, no. 41 (September 26, 2014): E4376—E4385. http://dx.doi.org/10.1073/pnas.1411649111.

Full text

APA, Harvard, Vancouver, ISO, and other styles

5

Holth, Jerrah K., Sarah K. Fritschi, Chanung Wang, Nigel P. Pedersen, John R. Cirrito, Thomas E. Mahan, Mary Beth Finn, et al. "The sleep-wake cycle regulates brain interstitial fluid tau in mice and CSF tau in humans." Science 363, no. 6429 (January 24, 2019): 880–84. http://dx.doi.org/10.1126/science.aav2546.

Full text

Abstract:

The sleep-wake cycle regulates interstitial fluid (ISF) and cerebrospinal fluid (CSF) levels of β-amyloid (Aβ) that accumulates in Alzheimer’s disease (AD). Furthermore, chronic sleep deprivation (SD) increases Aβ plaques. However, tau, not Aβ, accumulation appears to drive AD neurodegeneration. We tested whether ISF/CSF tau and tau seeding and spreading were influenced by the sleep-wake cycle and SD. Mouse ISF tau was increased ~90% during normal wakefulness versus sleep and ~100% during SD. Human CSF tau also increased more than 50% during SD. In a tau seeding-and-spreading model, chronic SD increased tau pathology spreading. Chemogenetically driven wakefulness in mice also significantly increased both ISF Aβ and tau. Thus, the sleep-wake cycle regulates ISF tau, and SD increases ISF and CSF tau as well as tau pathology spreading.

APA, Harvard, Vancouver, ISO, and other styles

6

Robert, Aiko, Michael Schöll, and Thomas Vogels. "Tau Seeding Mouse Models with Patient Brain-Derived Aggregates." International Journal of Molecular Sciences 22, no. 11 (June 7, 2021): 6132. http://dx.doi.org/10.3390/ijms22116132.

Full text

Abstract:

Tauopathies are a heterogeneous class of neurodegenerative diseases characterized by intracellular inclusions of aggregated tau proteins. Tau aggregates in different tauopathies have distinct structural features and can be found in different cell types. Transgenic animal models overexpressing human tau have been used for over two decades in the research of tau pathology. However, these models poorly recapitulate the heterogeneity of tauopathies found in human brains. Recent findings demonstrate that injection of purified tau aggregates from the brains of human tauopathy patients recapitulates both the structural features and cell-type specificity of the tau pathology of the donor tauopathy. These models may therefore have unique translational value in the study of functional consequences of tau pathology, tau-based diagnostics, and tau targeting therapeutics. This review provides an update of the literature relating to seeding-based tauopathy and their potential applications.

APA, Harvard, Vancouver, ISO, and other styles

7

Polanco, Juan Carlos, Yevhen Akimov, Avinash Fernandes, Adam Briner, Gabriel Rhys Hand, Marloes van Roijen, Giuseppe Balistreri, and Jürgen Götz. "CRISPRi screening reveals regulators of tau pathology shared between exosomal and vesicle-free tau." Life Science Alliance 6, no. 1 (October 31, 2022): e202201689. http://dx.doi.org/10.26508/lsa.202201689.

Full text

Abstract:

The aggregation of the microtubule-associated protein tau is a defining feature of Alzheimer’s disease and other tauopathies. Tau pathology is believed to be driven by free tau aggregates and tau carried within exosome-like extracellular vesicles, both of which propagate trans-synaptically and induce tau pathology in recipient neurons by a corrupting process of seeding. Here, we performed a genome-wide CRISPRi screen in tau biosensor cells and identified cellular regulators shared by both mechanisms of tau seeding. We identified ANKLE2, BANF1, NUSAP1, EIF1AD, and VPS18 as the top validated regulators that restrict tau aggregation initiated by both exosomal and vesicle-free tau seeds. None of our validated hits affected the uptake of either form of tau seeds, supporting the notion that they operate through a cell-autonomous mechanism downstream of the seed uptake. Lastly, validation studies with human brain tissue also revealed that several of the identified protein hits are down-regulated in the brains of Alzheimer’s patients, suggesting that their decreased activity may be required for the emergence or progression of tau pathology in the human brain.

APA, Harvard, Vancouver, ISO, and other styles

8

Abskharon, Romany, Paul M. Seidler, Michael R. Sawaya, Duilio Cascio, Tianxiao P. Yang, Stephan Philipp, Christopher Kazu Williams, et al. "Crystal structure of a conformational antibody that binds tau oligomers and inhibits pathological seeding by extracts from donors with Alzheimer's disease." Journal of Biological Chemistry 295, no. 31 (June 3, 2020): 10662–76. http://dx.doi.org/10.1074/jbc.ra120.013638.

Full text

Abstract:

Soluble oligomers of aggregated tau accompany the accumulation of insoluble amyloid fibrils, a histological hallmark of Alzheimer disease (AD) and two dozen related neurodegenerative diseases. Both oligomers and fibrils seed the spread of Tau pathology, and by virtue of their low molecular weight and relative solubility, oligomers may be particularly pernicious seeds. Here, we report the formation of in vitro tau oligomers formed by an ionic liquid (IL15). Using IL15-induced recombinant tau oligomers and a dot blot assay, we discovered a mAb (M204) that binds oligomeric tau, but not tau monomers or fibrils. M204 and an engineered single-chain variable fragment (scFv) inhibited seeding by IL15-induced tau oligomers and pathological extracts from donors with AD and chronic traumatic encephalopathy. This finding suggests that M204-scFv targets pathological structures that are formed by tau in neurodegenerative diseases. We found that M204-scFv itself partitions into oligomeric forms that inhibit seeding differently, and crystal structures of the M204-scFv monomer, dimer, and trimer revealed conformational differences that explain differences among these forms in binding and inhibition. The efficiency of M204-scFv antibodies to inhibit the seeding by brain tissue extracts from different donors with tauopathies varied among individuals, indicating the possible existence of distinct amyloid polymorphs. We propose that by binding to oligomers, which are hypothesized to be the earliest seeding-competent species, M204-scFv may have potential as an early-stage diagnostic for AD and tauopathies, and also could guide the development of promising therapeutic antibodies.

APA, Harvard, Vancouver, ISO, and other styles

9

Leyns, Cheryl E. G., Maud Gratuze, Sneha Narasimhan, Nimansha Jain, Lauren J. Koscal, Hong Jiang, Melissa Manis, et al. "TREM2 function impedes tau seeding in neuritic plaques." Nature Neuroscience 22, no. 8 (June 24, 2019): 1217–22. http://dx.doi.org/10.1038/s41593-019-0433-0.

Full text

APA, Harvard, Vancouver, ISO, and other styles

10

Ridler, Charlotte. "Tau seeding starts early in the entorhinal cortex." Nature Reviews Neurology 14, no. 7 (May 24, 2018): 380. http://dx.doi.org/10.1038/s41582-018-0016-9.

Full text

APA, Harvard, Vancouver, ISO, and other styles

11

Vigers, Michael, and Songi Han. "Proteolytic Fragments of tau Produce Seeding-Competent Fibrils." Biophysical Journal 118, no. 3 (February 2020): 541a. http://dx.doi.org/10.1016/j.bpj.2019.11.2963.

Full text

APA, Harvard, Vancouver, ISO, and other styles

12

Furman, Jennifer L., Jaime Vaquer-Alicea, Charles L. White, Nigel J. Cairns, Peter T. Nelson, and Marc I. Diamond. "Widespread tau seeding activity at early Braak stages." Acta Neuropathologica 133, no. 1 (November 22, 2016): 91–100. http://dx.doi.org/10.1007/s00401-016-1644-z.

Full text

APA, Harvard, Vancouver, ISO, and other styles

13

Tarutani, Airi, Haruka Miyata, Takashi Nonaka, Kazuko Hasegawa, Mari Yoshida, Yuko Saito, Shigeo Murayama, et al. "Human tauopathy-derived tau strains determine the substrates recruited for templated amplification." Brain 144, no. 8 (March 9, 2021): 2333–48. http://dx.doi.org/10.1093/brain/awab091.

Full text

Abstract:

Abstract Tauopathies are a subset of neurodegenerative diseases characterized by abnormal tau inclusions. Specifically, three-repeat tau and four-repeat tau in Alzheimer’s disease, three-repeat tau in Pick’s disease (PiD) and four-repeat tau in progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) form amyloid-like fibrous structures that accumulate in neurons and/or glial cells. Amplification and cell-to-cell transmission of abnormal tau based on the prion hypothesis are believed to explain the onset and progression of tauopathies. Recent studies support not only the self-propagation of abnormal tau, but also the presence of conformationally distinct tau aggregates, namely tau strains. Cryogenic electron microscopy analyses of patient-derived tau filaments have revealed disease-specific ordered tau structures. However, it remains unclear whether the ultrastructural and biochemical properties of tau strains are inherited during the amplification of abnormal tau in the brain. In this study, we investigated template-dependent amplification of tau aggregates using a cellular model of seeded aggregation. Tau strains extracted from human tauopathies caused strain-dependent accumulation of insoluble filamentous tau in SH-SY5Y cells. The seeding activity towards full-length four-repeat tau substrate was highest in CBD-tau seeds, followed by PSP-tau and Alzheimer’s disease (AD)-tau seeds, while AD-tau seeds showed higher seeding activity than PiD-tau seeds towards three-repeat tau substrate. Abnormal tau amplified in cells inherited the ultrastructural and biochemical properties of the original seeds. These results strongly suggest that the structural differences of patient-derived tau strains underlie the diversity of tauopathies, and that seeded aggregation and filament formation mimicking the pathogenesis of sporadic tauopathy can be reproduced in cultured cells. Our results indicate that the disease-specific conformation of tau aggregates determines the tau isoform substrate that is recruited for templated amplification, and also influences the prion-like seeding activity.

APA, Harvard, Vancouver, ISO, and other styles

14

Soares, Alberto Carpinteiro, Andreia Ferreira, Jonas Mariën, Charlotte Delay, Edward Lee, John Q. Trojanowski, Dieder Moechars, Wim Annaert, and Louis De Muynck. "PIKfyve activity is required for lysosomal trafficking of tau aggregates and tau seeding." Journal of Biological Chemistry 296 (January 2021): 100636. http://dx.doi.org/10.1016/j.jbc.2021.100636.

Full text

APA, Harvard, Vancouver, ISO, and other styles

15

Rosenqvist, Nina, Ayodeji A. Asuni, Christian R. Andersson, Søren Christensen, Justus A. Daechsel, Jan Egebjerg, Jeppe Falsig, et al. "Highly specific and selective anti‐pS396‐tau antibody C10.2 targets seeding‐competent tau." Alzheimer's & Dementia: Translational Research & Clinical Interventions 4, no. 1 (January 2018): 521–34. http://dx.doi.org/10.1016/j.trci.2018.09.005.

Full text

APA, Harvard, Vancouver, ISO, and other styles

16

Manos, Justine D., Christina N. Preiss, Nandini Venkat, Joseph Tamm, Peter Reinhardt, Taekyung Kwon, Jessica Wu, et al. "Uncovering specificity of endogenous TAU aggregation in a human iPSC-neuron TAU seeding model." iScience 25, no. 1 (January 2022): 103658. http://dx.doi.org/10.1016/j.isci.2021.103658.

Full text

APA, Harvard, Vancouver, ISO, and other styles

17

Albert, Marie, Georges Mairet-Coello, Clément Danis, Sarah Lieger, Raphaëlle Caillierez, Sébastien Carrier, Emilie Skrobala, et al. "Prevention of tau seeding and propagation by immunotherapy with a central tau epitope antibody." Brain 142, no. 6 (April 30, 2019): 1736–50. http://dx.doi.org/10.1093/brain/awz100.

Full text

APA, Harvard, Vancouver, ISO, and other styles

18

Guo, Jing L., and Virginia M. Y. Lee. "Seeding of Normal Tau by Pathological Tau Conformers Drives Pathogenesis of Alzheimer-like Tangles." Journal of Biological Chemistry 286, no. 17 (March 3, 2011): 15317–31. http://dx.doi.org/10.1074/jbc.m110.209296.

Full text

APA, Harvard, Vancouver, ISO, and other styles

19

Sigurdsson, Einar M., Erin Elizabeth Congdon, Jiaping Gu, and Suhail Rasool. "P4-229: TAU ANTIBODY-MEDIATED PREVENTION OF SEEDING OF TAU PATHOLOGY AND ASSOCIATED TOXICITY." Alzheimer's & Dementia 10 (July 2014): P871. http://dx.doi.org/10.1016/j.jalz.2014.05.1747.

Full text

APA, Harvard, Vancouver, ISO, and other styles

20

Stopschinski, Barbara E., Talitha L. Thomas, Sourena Nadji, Eric Darvish, Linfeng Fan, Brandon B. Holmes, Anuja R. Modi, et al. "A synthetic heparinoid blocks Tau aggregate cell uptake and amplification." Journal of Biological Chemistry 295, no. 10 (January 23, 2020): 2974–83. http://dx.doi.org/10.1074/jbc.ra119.010353.

Full text

Abstract:

Tau aggregation underlies neurodegeneration in Alzheimer's disease and related tauopathies. We and others have proposed that transcellular propagation of pathology is mediated by Tau prions, which are ordered protein assemblies that faithfully replicate in vivo and cause specific biological effects. The prion model predicts the release of aggregates from a first-order cell and subsequent uptake into a second-order cell. The assemblies then serve as templates for their own replication, a process termed “seeding.” We have previously observed that heparan sulfate proteoglycans on the cell surface mediate the cellular uptake of Tau aggregates. This interaction is blocked by heparin, a sulfated glycosaminoglycan. Indeed, heparin-like molecules, or heparinoids, have previously been proposed as a treatment for PrP prion disorders. However, heparin is not ideal for managing chronic neurodegeneration, because it is difficult to synthesize in defined sizes, may have poor brain penetration because of its negative charge, and is a powerful anticoagulant. Therefore, we sought to generate an oligosaccharide that would bind Tau and block its cellular uptake and seeding, without exhibiting anticoagulation activity. We created a compound, SN7–13, from pentasaccharide units and tested it in a range of assays that measured direct binding of Tau to glycosaminoglycans and inhibition of Tau uptake and seeding in cells. SN7–13 does not inhibit coagulation, binds Tau with low nanomolar affinity, and inhibits cellular Tau aggregate propagation similarly to standard porcine heparin. This synthetic heparinoid could facilitate the development of agents to treat tauopathy.

APA, Harvard, Vancouver, ISO, and other styles

21

Kaufman, Sarah K., Sarah Svirsky, Jonathan D. Cherry, Ann C. McKee, and Marc I. Diamond. "Tau seeding in chronic traumatic encephalopathy parallels disease severity." Acta Neuropathologica 142, no. 6 (October 9, 2021): 951–60. http://dx.doi.org/10.1007/s00401-021-02373-5.

Full text

APA, Harvard, Vancouver, ISO, and other styles

22

McEwan, William A., Benjamin Falcon, Marina Vaysburd, Dean Clift, Adrian L. Oblak, Bernardino Ghetti, Michel Goedert, and Leo C. James. "Cytosolic Fc receptor TRIM21 inhibits seeded tau aggregation." Proceedings of the National Academy of Sciences 114, no. 3 (January 3, 2017): 574–79. http://dx.doi.org/10.1073/pnas.1607215114.

Full text

Abstract:

Alzheimer’s disease (AD) and other neurodegenerative disorders are associated with the cytoplasmic aggregation of microtubule-associated protein tau. Recent evidence supports transcellular transfer of tau misfolding (seeding) as the mechanism of spread within an affected brain, a process reminiscent of viral infection. However, whereas microbial pathogens can be recognized as nonself by immune receptors, misfolded protein assemblies evade detection, as they are host-derived. Here, we show that when misfolded tau assemblies enter the cell, they can be detected and neutralized via a danger response mediated by tau-associated antibodies and the cytosolic Fc receptor tripartite motif protein 21 (TRIM21). We developed fluorescent, morphology-based seeding assays that allow the formation of pathological tau aggregates to be measured in situ within 24 h in the presence of picomolar concentrations of tau seeds. We found that anti-tau antibodies accompany tau seeds into the cell, where they recruit TRIM21 shortly after entry. After binding, TRIM21 neutralizes tau seeds through the activity of the proteasome and the AAA ATPase p97/VCP in a similar manner to infectious viruses. These results establish that intracellular antiviral immunity can be redirected against host-origin endopathogens involved in neurodegeneration.

APA, Harvard, Vancouver, ISO, and other styles

23

Song, Liqing, Daniel E. Oseid, Evan A. Wells, and Anne Skaja Robinson. "The Interplay between GSK3β and Tau Ser262 Phosphorylation during the Progression of Tau Pathology." International Journal of Molecular Sciences 23, no. 19 (October 1, 2022): 11610. http://dx.doi.org/10.3390/ijms231911610.

Full text

Abstract:

Tau hyperphosphorylation has been linked directly to the formation of toxic neurofibrillary tangles (NFTs) in tauopathies, however, prior to NFT formation, the sequence of pathological events involving tau phosphorylation remains unclear. Here, the effect of glycogen synthase kinase 3β (GSK3β) on tau pathology was examined independently for each step of transcellular propagation; namely, tau intracellular aggregation, release, cellular uptake and seeding activity. We find that overexpression of GSK3β-induced phosphorylated 0N4R tau led to a higher level of tau oligomerization in SH-SY5Y neuroblastoma cells than wild type 0N4R, as determined by several orthogonal assays. Interestingly, the presence of GSK3β also enhanced tau release. Further, we demonstrated that cells endocytosed more monomeric tau protein when pre-phosphorylated by GSK3β. Using an extracellular vesicle (EVs)-assisted tau neuronal delivery system, we show that exosomal GSK3β-phosphorylated tau, when added to differentiated SH-SY5Y cells, induced more efficient tau transfer, showing much higher total tau levels and increased tau aggregate formation as compared to wild type exosomal tau. The role of a primary tau phosphorylation site targeted by microtubule-affinity regulating kinases (MARKs), Ser262, was tested by pseudo-phosphorylation using site-directed mutagenesis to aspartate (S262D). S262D tau overexpression significantly enhanced tau release and intracellular tau accumulation, which were concurrent with the increase of pathological states of tau, as determined by immunodetection. Importantly, phosphorylation-induced tau accumulation was augmented by co-transfecting S262D tau with GSK3β, suggesting a possible interplay between Ser262 phosphorylation and GSK3β activity in tau pathology. Lastly, we found that pre-treatment of cells with amyloid-β (Aβ) further tau phosphorylation and accumulation when Ser262 pre-phosphorylation was present, suggesting that S262 may be a primary mediator of Aβ-induced tau toxicity. These findings provide a potential therapeutic target for treating tau-related disorders by targeting specific phospho-tau isoforms and further elucidate the GSK3β-mediated pathological seeding mechanisms.

APA, Harvard, Vancouver, ISO, and other styles

24

Fichou, Yann, Yanxian Lin, Jennifer N. Rauch, Michael Vigers, Zhikai Zeng, Madhur Srivastava, Timothy J. Keller, Jack H. Freed, Kenneth S. Kosik, and Songi Han. "Cofactors are essential constituents of stable and seeding-active tau fibrils." Proceedings of the National Academy of Sciences 115, no. 52 (December 11, 2018): 13234–39. http://dx.doi.org/10.1073/pnas.1810058115.

Full text

Abstract:

Amyloid fibrils are cross-β–rich aggregates that are exceptionally stable forms of protein assembly. Accumulation of tau amyloid fibrils is involved in many neurodegenerative diseases, including Alzheimer’s disease (AD). Heparin-induced aggregates have been widely used and assumed to be a good tau amyloid fibril model for most biophysical studies. Here we show that mature fibrils made of 4R tau variants, prepared with heparin or RNA, spontaneously depolymerize and release monomers when their cofactors are removed. We demonstrate that the cross-β-sheet assembly formed in vitro with polyanion addition is unstable at room temperature. We furthermore demonstrate high seeding capacity with transgenic AD mouse brain-extracted tau fibrils in vitro that, however, is exhausted after one generation, while supplementation with RNA cofactors resulted in sustained seeding over multiple generations. We suggest that tau fibrils formed in brains are supported by unknown cofactors and inhere higher-quality packing, as reflected in a more distinct conformational arrangement in the mouse fibril-seeded, compared with heparin-induced, tau fibrils. Our study suggests that the role of cofactors in tauopathies is a worthy focus of future studies, as they may be viable targets for diagnosis and therapeutics.

APA, Harvard, Vancouver, ISO, and other styles

25

Cooper, Joanna M., Aurelien Lathuiliere, Mary Migliorini, Allison L. Arai, Mashhood M. Wani, Simon Dujardin, Selen C. Muratoglu, Bradley T. Hyman, and Dudley K. Strickland. "Regulation of tau internalization, degradation, and seeding by LRP1 reveals multiple pathways for tau catabolism." Journal of Biological Chemistry 296 (January 2021): 100715. http://dx.doi.org/10.1016/j.jbc.2021.100715.

Full text

APA, Harvard, Vancouver, ISO, and other styles

26

Van Kolen, Kristof, Thomas J. Malia, Clara Theunis, Rupesh Nanjunda, Alexey Teplyakov, Robin Ernst, Sheng-Jiun Wu, et al. "Discovery and Functional Characterization of hPT3, a Humanized Anti-Phospho Tau Selective Monoclonal Antibody." Journal of Alzheimer's Disease 77, no. 4 (October 13, 2020): 1397–416. http://dx.doi.org/10.3233/jad-200544.

Full text

Abstract:

Background: As a consequence of the discovery of an extracellular component responsible for the progression of tau pathology, tau immunotherapy is being extensively explored in both preclinical and clinical studies as a disease modifying strategy for the treatment of Alzheimer’s disease. Objective: Describe the characteristics of the anti-phospho (T212/T217) tau selective antibody PT3 and its humanized variant hPT3. Methods: By performing different immunization campaigns, a large collection of antibodies has been generated and prioritized. In depth, in vitro characterization using surface plasmon resonance, phospho-epitope mapping, and X-ray crystallography experiments were performed. Further characterization involved immunohistochemical staining on mouse- and human postmortem tissue and neutralization of tau seeding by immunodepletion assays. Results and Conclusion: Various in vitro experiments demonstrated a high intrinsic affinity for PT3 and hPT3 for AD brain-derived paired helical filaments but also to non-aggregated phospho (T212/T217) tau. Further functional analyses in cellular and in vivo models of tau seeding demonstrated almost complete depletion of tau seeds in an AD brain homogenate. Ongoing trials will provide the clinical evaluation of the tau spreading hypothesis in Alzheimer’s disease.

APA, Harvard, Vancouver, ISO, and other styles

27

Vasconcelos, Bruno, Ilie-Cosmin Stancu, Arjan Buist, Matthew Bird, Peng Wang, Alexandre Vanoosthuyse, Kristof Van Kolen, et al. "Heterotypic seeding of Tau fibrillization by pre-aggregated Abeta provides potent seeds for prion-like seeding and propagation of Tau-pathology in vivo." Acta Neuropathologica 131, no. 4 (January 6, 2016): 549–69. http://dx.doi.org/10.1007/s00401-015-1525-x.

Full text

APA, Harvard, Vancouver, ISO, and other styles

28

Pérez, Mar, Miguel Medina, Félix Hernández, and Jesús Avila. "Secretion of full-length Tau or Tau fragments in cell culture models. Propagation of Tau in vivo and in vitro." Biomolecular Concepts 9, no. 1 (March 5, 2018): 1–11. http://dx.doi.org/10.1515/bmc-2018-0001.

Full text

Abstract:

AbstractThe microtubule-associated protein Tau plays a crucial role in stabilizing neuronal microtubules. In Tauopathies, Tau loses its ability to bind microtubules, detach from them and forms intracellular aggregates. Increasing evidence in recent years supports the notion that Tau pathology spreading throughout the brain in AD and other Tauopathies is the consequence of the propagation of specific Tau species along neuroanatomically connected brain regions in a so-called “prion-like” manner. A number of steps are assumed to be involved in this process, including secretion, cellular uptake, transcellular transfer and/or seeding, although the precise mechanisms underlying propagation of Tau pathology are not fully understood yet. This review summarizes recent evidence on the nature of the specific Tau species that are propagated and the different mechanisms of Tau pathology spreading.

APA, Harvard, Vancouver, ISO, and other styles

29

Ferrer, Isidro, Pol Andrés-Benito, Paula Garcia-Esparcia, Irene López-Gonzalez, Diego Valiente, Mónica Jordán-Pirla, Margarita Carmona, Julia Sala-Jarque, Vanessa Gil, and José Antonio del Rio. "Differences in Tau Seeding in Newborn and Adult Wild-Type Mice." International Journal of Molecular Sciences 23, no. 9 (April 26, 2022): 4789. http://dx.doi.org/10.3390/ijms23094789.

Full text

Abstract:

Alzheimer’s disease (AD) and other tauopathies are common neurodegenerative diseases in older adults; in contrast, abnormal tau deposition in neurons and glial cells occurs only exceptionally in children. Sarkosyl-insoluble fractions from sporadic AD (sAD) containing paired helical filaments (PHFs) were inoculated unilaterally into the thalamus in newborn and three-month-old wild-type C57BL/6 mice, which were killed at different intervals from 24 h to six months after inoculation. Tau-positive cells were scanty and practically disappeared at three months in mice inoculated at the age of a newborn. In contrast, large numbers of tau-positive cells, including neurons and oligodendrocytes, were found in the thalamus of mice inoculated at three months and killed at the ages of six months and nine months. Mice inoculated at the age of newborn and re-inoculated at the age of three months showed similar numbers and distribution of positive cells in the thalamus at six months and nine months. This study shows that (a) differences in tau seeding between newborn and young adults may be related to the ratios between 3Rtau and 4Rtau, and the shift to 4Rtau predominance in adults, together with the immaturity of connections in newborn mice, and (b) intracerebral inoculation of sAD PHFs in newborn mice does not protect from tau seeding following intracerebral inoculation of sAD PHFs in young/adult mice.

APA, Harvard, Vancouver, ISO, and other styles

30

Guo, Jing L., Sneha Narasimhan, Lakshmi Changolkar, Zhuohao He, Anna Stieber, Bin Zhang, Ronald J. Gathagan, et al. "Unique pathological tau conformers from Alzheimer’s brains transmit tau pathology in nontransgenic mice." Journal of Experimental Medicine 213, no. 12 (October 17, 2016): 2635–54. http://dx.doi.org/10.1084/jem.20160833.

Full text

Abstract:

Filamentous tau aggregates are hallmark lesions in numerous neurodegenerative diseases, including Alzheimer’s disease (AD). Cell culture and animal studies showed that tau fibrils can undergo cell-to-cell transmission and seed aggregation of soluble tau, but this phenomenon was only robustly demonstrated in models overexpressing tau. In this study, we found that intracerebral inoculation of tau fibrils purified from AD brains (AD-tau), but not synthetic tau fibrils, resulted in the formation of abundant tau inclusions in anatomically connected brain regions in nontransgenic mice. Recombinant human tau seeded by AD-tau revealed unique conformational features that are distinct from synthetic tau fibrils, which could underlie the differential potency in seeding physiological levels of tau to aggregate. Therefore, our study establishes a mouse model of sporadic tauopathies and points to important differences between tau fibrils that are generated artificially and authentic ones that develop in AD brains.

APA, Harvard, Vancouver, ISO, and other styles

31

Heinsen, Helmut, and Lea T. Grinberg. "On the origin of tau seeding activity in Alzheimer’s disease." Acta Neuropathologica 136, no. 5 (July 23, 2018): 815–17. http://dx.doi.org/10.1007/s00401-018-1890-3.

Full text

APA, Harvard, Vancouver, ISO, and other styles

32

Nachman, Eliana, Anne S. Wentink, Karine Madiona, Luc Bousset, Taxiarchis Katsinelos, Kieren Allinson, Harm Kampinga, et al. "Disassembly of Tau fibrils by the human Hsp70 disaggregation machinery generates small seeding-competent species." Journal of Biological Chemistry 295, no. 28 (May 28, 2020): 9676–90. http://dx.doi.org/10.1074/jbc.ra120.013478.

Full text

Abstract:

The accumulation of amyloid Tau aggregates is implicated in Alzheimer's disease (AD) and other tauopathies. Molecular chaperones are known to maintain protein homeostasis. Here, we show that an ATP-dependent human chaperone system disassembles Tau fibrils in vitro. We found that this function is mediated by the core chaperone HSC70, assisted by specific cochaperones, in particular class B J-domain proteins and a heat shock protein 110 (Hsp110)-type nucleotide exchange factor (NEF). The Hsp70 disaggregation machinery processed recombinant fibrils assembled from all six Tau isoforms as well as Sarkosyl-resistant Tau aggregates extracted from cell cultures and human AD brain tissues, demonstrating the ability of the Hsp70 machinery to recognize a broad range of Tau aggregates. However, the chaperone activity released monomeric and small oligomeric Tau species, which induced the aggregation of self-propagating Tau conformers in a Tau cell culture model. We conclude that the activity of the Hsp70 disaggregation machinery is a double-edged sword, as it eliminates Tau amyloids at the cost of generating new seeds.

APA, Harvard, Vancouver, ISO, and other styles

33

Ledreux, Aurélie, Sarah Thomas, Eric D. Hamlett, Camille Trautman, Anah Gilmore, Emily Rickman Hager, Daniel A. Paredes, Martin Margittai, Juan Fortea, and Ann-Charlotte Granholm. "Small Neuron-Derived Extracellular Vesicles from Individuals with Down Syndrome Propagate Tau Pathology in the Wildtype Mouse Brain." Journal of Clinical Medicine 10, no. 17 (August 31, 2021): 3931. http://dx.doi.org/10.3390/jcm10173931.

Full text

Abstract:

Individuals with Down syndrome (DS) exhibit Alzheimer’s disease (AD) pathology at a young age, including amyloid plaques and neurofibrillary tangles (NFTs). Tau pathology can spread via extracellular vesicles, such as exosomes. The cargo of neuron-derived small extracellular vesicles (NDEVs) from individuals with DS contains p-Tau at an early age. The goal of the study was to investigate whether NDEVs isolated from the blood of individuals with DS can spread Tau pathology in the brain of wildtype mice. We purified NDEVs from the plasma of patients with DS-AD and controls and injected small quantities using stereotaxic surgery into the dorsal hippocampus of adult wildtype mice. Seeding competent Tau conformers were amplified in vitro from DS-AD NDEVs but not NDEVs from controls. One month or 4 months post-injection, we examined Tau pathology in mouse brains. We found abundant p-Tau immunostaining in the hippocampus of the mice injected with DS-AD NDEVs compared to injections of age-matched control NDEVs. Double labeling with neuronal and glial markers showed that p-Tau staining was largely found in neurons and, to a lesser extent, in glial cells and that p-Tau immunostaining was spreading along the corpus callosum and the medio-lateral axis of the hippocampus. These studies demonstrate that NDEVs from DS-AD patients exhibit Tau seeding capacity and give rise to tangle-like intracellular inclusions.

APA, Harvard, Vancouver, ISO, and other styles

34

DeVos, Sarah L., Rebecca L. Miller, Kathleen M. Schoch, Brandon B. Holmes, Carey S. Kebodeaux, Amy J. Wegener, Guo Chen, et al. "Tau reduction prevents neuronal loss and reverses pathological tau deposition and seeding in mice with tauopathy." Science Translational Medicine 9, no. 374 (January 25, 2017): eaag0481. http://dx.doi.org/10.1126/scitranslmed.aag0481.

Full text

APA, Harvard, Vancouver, ISO, and other styles

35

Ferrer, Isidro, Pol Andrés-Benito, Margarita Carmona, and José Antonio del Rio. "Common and Specific Marks of Different Tau Strains Following Intra-Hippocampal Injection of AD, PiD, and GGT Inoculum in hTau Transgenic Mice." International Journal of Molecular Sciences 23, no. 24 (December 14, 2022): 15940. http://dx.doi.org/10.3390/ijms232415940.

Full text

Abstract:

Heterozygous hTau mice were used for the study of tau seeding. These mice express the six human tau isoforms, with a high predominance of 3Rtau over 4Rtau. The following groups were assessed: (i) non-inoculated mice aged 9 months (n = 4); (ii) Alzheimer’s Disease (AD)-inoculated mice (n = 4); (iii) Globular Glial Tauopathy (GGT)-inoculated mice (n = 4); (iv) Pick’s disease (PiD)-inoculated mice (n = 4); (v) control-inoculated mice (n = 4); and (vi) inoculated with vehicle alone (n = 2). AD-inoculated mice showed AT8-immunoreactive neuronal pre-tangles, granular aggregates, and dots in the CA1 region of the hippocampus, dentate gyrus (DG), and hilus, and threads and dots in the ipsilateral corpus callosum. GGT-inoculated mice showed unique or multiple AT8-immunoreactive globular deposits in neurons, occasionally extended to the proximal dendrites. PiD-inoculated mice showed a few loose pre-tangles in the CA1 region, DG, and cerebral cortex near the injection site. Coiled bodies were formed in the corpus callosum in AD-inoculated mice, but GGT-inoculated mice lacked globular glial inclusions. Tau deposits in inoculated mice co-localized active kinases p38-P and SAPK/JNK-P, thus suggesting active phosphorylation of the host tau. Tau deposits were absent in hTau mice inoculated with control homogenates and vehicle alone. Deposits in AD-inoculated hTau mice contained 3Rtau and 4Rtau; those in GGT-inoculated mice were mainly stained with anti-4Rtau antibodies, but a small number of deposits contained 3Rtau. Deposits in PiD-inoculated mice were stained with anti-3Rtau antibodies, but rare neuronal, thread-like, and dot-like deposits showed 4Rtau immunoreactivity. These findings show that tau strains produce different patterns of active neuronal seeding, which also depend on the host tau. Unexpected 3Rtau and 4Rtau deposits after inoculation of homogenates from 4R and 3R tauopathies, respectively, suggests the regulation of exon 10 splicing of the host tau during the process of seeding, thus modulating the plasticity of the cytoskeleton.

APA, Harvard, Vancouver, ISO, and other styles

36

Ghag, Gaurav, Nemil Bhatt, Daniel V. Cantu, Marcos J. Guerrero-Munoz, Anna Ellsworth, Urmi Sengupta, and Rakez Kayed. "Soluble tau aggregates, not large fibrils, are the toxic species that display seeding and cross-seeding behavior." Protein Science 27, no. 11 (October 19, 2018): 1901–9. http://dx.doi.org/10.1002/pro.3499.

Full text

APA, Harvard, Vancouver, ISO, and other styles

37

Annadurai, Narendran, Lukáš Malina, Mario Salmona, Luisa Diomede, Antonio Bastone, Alfredo Cagnotto, Margherita Romeo, et al. "Antitumour drugs targeting tau R3 VQIVYK and Cys322 prevent seeding of endogenous tau aggregates by exogenous seeds." FEBS Journal 289, no. 7 (November 18, 2021): 1929–49. http://dx.doi.org/10.1111/febs.16270.

Full text

APA, Harvard, Vancouver, ISO, and other styles

38

Danis, Clément, Elian Dupré, Orgeta Zejneli, Raphaëlle Caillierez, Alexis Arrial, Séverine Bégard, Justine Mortelecque, et al. "Inhibition of Tau seeding by targeting Tau nucleation core within neurons with a single domain antibody fragment." Molecular Therapy 30, no. 4 (April 2022): 1484–99. http://dx.doi.org/10.1016/j.ymthe.2022.01.009.

Full text

APA, Harvard, Vancouver, ISO, and other styles

39

Bajracharya, Rinie, David Brici, Jürgen Götz, and Rebecca M. Nisbet. "P4-036: NOVEL TAU-SPECIFIC MONOCLONAL ANTIBODY REDUCES TAU SEEDING AND ENHANCES PHAGOCYTIC ACTIVITY OF MICROGLIAL CELLS." Alzheimer's & Dementia 15 (July 2019): P1288. http://dx.doi.org/10.1016/j.jalz.2019.06.3695.

Full text

APA, Harvard, Vancouver, ISO, and other styles

40

Falcon, Benjamin, Annalisa Cavallini, Rachel Angers, Sarah Glover, Tracey K. Murray, Luanda Barnham, Samuel Jackson, et al. "Conformation Determines the Seeding Potencies of Native and Recombinant Tau Aggregates." Journal of Biological Chemistry 290, no. 2 (November 18, 2014): 1049–65. http://dx.doi.org/10.1074/jbc.m114.589309.

Full text

APA, Harvard, Vancouver, ISO, and other styles

41

Yanamandra, Kiran, Najla Kfoury, Hong Jiang, Thomas E. Mahan, Shengmei Ma, Susan E. Maloney, David F. Wozniak, Marc I. Diamond, and David M. Holtzman. "Anti-Tau Antibodies that Block Tau Aggregate Seeding In Vitro Markedly Decrease Pathology and Improve Cognition In Vivo." Neuron 80, no. 2 (October 2013): 402–14. http://dx.doi.org/10.1016/j.neuron.2013.07.046.

Full text

APA, Harvard, Vancouver, ISO, and other styles

42

Yanamandra, Kiran, Najla Kfoury, Hong Jiang, Thomas E. Mahan, Shengmei Ma, Susan E. Maloney, David F. Wozniak, Marc I. Diamond, and David M. Holtzman. "Anti-Tau Antibodies that Block Tau Aggregate Seeding In Vitro Markedly Decrease Pathology and Improve Cognition In Vivo." Neuron 80, no. 6 (December 2013): 1572. http://dx.doi.org/10.1016/j.neuron.2013.12.007.

Full text

APA, Harvard, Vancouver, ISO, and other styles

43

Falcon, Benjamin, Annalisa Cavallini, Suchira Bose, and Michel Goedert. "P1-004: IDENTIFICATION OF TAU SPECIES REQUIRED FOR SEEDING IN A CELL-BASED MODEL OF PATHOLOGICAL TAU PROPAGATION." Alzheimer's & Dementia 10 (July 2014): P305—P306. http://dx.doi.org/10.1016/j.jalz.2014.05.239.

Full text

APA, Harvard, Vancouver, ISO, and other styles

44

Bose, Suchira, Annalisa Cavallini, Caroline Kerridge, Jane Cooper, Samuel J. Jackson, Alessia Landi, Claire V. Cella, et al. "O4-04-02: Characterisation of Tau Species Involved in Tau Seeding and Spread in Cellular and Animal Models." Alzheimer's & Dementia 12 (July 2016): P340. http://dx.doi.org/10.1016/j.jalz.2016.06.625.

Full text

APA, Harvard, Vancouver, ISO, and other styles

45

Atsmon-Raz, Yoav, and Yifat Miller. "Insight into Atomic Resolution of the Cross-Seeding between Tau/Mutated Tau and Amyloid-β in Neurodegenerative Diseases." Israel Journal of Chemistry 55, no. 6-7 (April 15, 2015): 628–36. http://dx.doi.org/10.1002/ijch.201400162.

Full text

APA, Harvard, Vancouver, ISO, and other styles

46

Makwana, Kamlesh M., Matthew P. Sarnowski, Jiayuan Miao, Yu-Shan Lin, and Juan R. Del Valle. "N-Amination Converts Amyloidogenic Tau Peptides into Soluble Antagonists of Cellular Seeding." ACS Chemical Neuroscience 12, no. 20 (October 5, 2021): 3928–38. http://dx.doi.org/10.1021/acschemneuro.1c00528.

Full text

APA, Harvard, Vancouver, ISO, and other styles

47

Qi, Ruxi, Yin Luo, Guanghong Wei, Ruth Nussinov, and Buyong Ma. "Aβ “Stretching-and-Packing” Cross-Seeding Mechanism Can Trigger Tau Protein Aggregation." Journal of Physical Chemistry Letters 6, no. 16 (August 7, 2015): 3276–82. http://dx.doi.org/10.1021/acs.jpclett.5b01447.

Full text

APA, Harvard, Vancouver, ISO, and other styles

48

Kraus, Allison, Eri Saijo, Michael A. Metrick, Kathy Newell, Christina J. Sigurdson, Gianluigi Zanusso, Bernardino Ghetti, and Byron Caughey. "Seeding selectivity and ultrasensitive detection of tau aggregate conformers of Alzheimer disease." Acta Neuropathologica 137, no. 4 (December 20, 2018): 585–98. http://dx.doi.org/10.1007/s00401-018-1947-3.

Full text

APA, Harvard, Vancouver, ISO, and other styles

49

Manca, Matteo, and Allison Kraus. "Defining the Protein Seeds of Neurodegeneration using Real-Time Quaking-Induced Conversion Assays." Biomolecules 10, no. 9 (August 25, 2020): 1233. http://dx.doi.org/10.3390/biom10091233.

Full text

Abstract:

Neurodegenerative diseases are characterized by the accumulation of disease-related misfolded proteins. It is now widely understood that the characteristic self-amplifying (i.e., seeding) capacity once only attributed to the prions of transmissible spongiform encephalopathy diseases is a feature of other misfolded proteins of neurodegenerative diseases, including tau, Aβ, and αSynuclein (αSyn). Ultrasensitive diagnostic assays, known as real-time quaking-induced conversion (RT-QuIC) assays, exploit these seeding capabilities in order to exponentially amplify protein seeds from various biospecimens. To date, RT-QuIC assays have been developed for the detection of protein seeds related to known prion diseases of mammals, the αSyn aggregates of Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy, and the tau aggregates of Alzheimer’s disease, chronic traumatic encephalopathy, and other tauopathies including progressive supranuclear palsy. Application of these assays to premortem human biospecimens shows promise for diagnosis of neurodegenerative disease and is an area of active investigation. RT-QuIC assays are also powerful experimental tools that can be used to dissect seeding networks within and between tissues and to evaluate how protein seed distribution and quantity correlate to disease-related outcomes in a host. As well, RT-QuIC application may help characterize molecular pathways influencing protein seed accumulation, transmission, and clearance. In this review we discuss the application of RT-QuIC assays as diagnostic, experimental, and structural tools for detection and discrimination of PrP prions, tau, and αSyn protein seeds.

APA, Harvard, Vancouver, ISO, and other styles

50

Stopschinski, Barbara E., Kelly Del Tredici, Sandi-Jo Estill-Terpack, Estifanos Ghebremdehin, Fang F. Yu, Heiko Braak, and Marc I. Diamond. "Anatomic survey of seeding in Alzheimer’s disease brains reveals unexpected patterns." Acta Neuropathologica Communications 9, no. 1 (October 11, 2021). http://dx.doi.org/10.1186/s40478-021-01255-x.

Full text

Abstract:

AbstractTauopathies are heterogeneous neurodegenerative diseases defined by progressive brain accumulation of tau aggregates. The most common tauopathy, sporadic Alzheimer’s disease (AD), involves progressive tau deposition that can be divided into specific stages of neurofibrillary tangle pathology. This classification is consistent with experimental data which suggests that network-based propagation is mediated by cell–cell transfer of tau “seeds”, or assemblies, that serve as templates for their own replication. Until now, seeding assays of AD brain have largely been limited to areas previously defined by NFT pathology. We now expand this work to additional regions. We selected 20 individuals with AD pathology of NFT stages I, III, and V. We stained and classified 25 brain regions in each using the anti-phospho-tau monoclonal antibody AT8. We measured tau seeding in each of the 500 samples using a cell-based tau “biosensor” assay in which induction of intracellular tau aggregation is mediated by exogenous tau assemblies. We observed a progressive increase in tau seeding according to NFT stage. Seeding frequently preceded NFT pathology, e.g., in the basolateral subnucleus of the amygdala and the substantia nigra, pars compacta. We observed seeding in brain regions not previously known to develop tau pathology, e.g., the globus pallidus and internal capsule, where AT8 staining revealed mainly axonal accumulation of tau. AT8 staining in brain regions identified because of tau seeding also revealed pathology in a previously undescribed cell type: Bergmann glia of the cerebellar cortex. We also detected tau seeding in brain regions not previously examined, e.g., the intermediate reticular zone, dorsal raphe nucleus, amygdala, basal nucleus of Meynert, and olfactory bulb. In conclusion, tau histopathology and seeding are complementary analytical tools. Tau seeding assays reveal pathology in the absence of AT8 signal in some instances, and previously unrecognized sites of tau deposition. The variation in sites of seeding between individuals could underlie differences in the clinical presentation and course of AD.

APA, Harvard, Vancouver, ISO, and other styles

We offer discounts on all premium plans for authors whose works are included in thematic literature selections. Contact us to get a unique promo code!